Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19

Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Meletiadis, Joseph [verfasserIn] Tsiodras, Sotirios [verfasserIn] Tsirigotis, Panagiotis [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	COVID-19 Cytokine storm IL6 blocking JAK-STAT inhibitors Ruxolitinib Sarilumab Severe respiratory syndrome Siltuximab Tocilizumab

Übergeordnetes Werk:	Enthalten in: Infectious diseases and therapy - Heidelberg : Springer, 2012, 9(2020), 4 vom: 12. Aug., Seite 707-713
Übergeordnetes Werk:	volume:9 ; year:2020 ; number:4 ; day:12 ; month:08 ; pages:707-713

Links:	Volltext

DOI / URN:	10.1007/s40121-020-00326-1

Katalog-ID:	SPR042044030

Internformat


LEADER	01000caa a22002652 4500
001	SPR042044030
003	DE-627
005	20230519234052.0
007	cr uuu---uuuuu
008	201122s2020 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1007/s40121-020-00326-1 \|2 doi
035			\|a (DE-627)SPR042044030
035			\|a (SPR)s40121-020-00326-1-e
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
082	0	4	\|a 610 \|q ASE
100	1		\|a Meletiadis, Joseph \|e verfasserin \|4 aut
245	1	0	\|a Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19
264		1	\|c 2020
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial.
650		4	\|a COVID-19 \|7 (dpeaa)DE-He213
650		4	\|a Cytokine storm \|7 (dpeaa)DE-He213
650		4	\|a IL6 blocking \|7 (dpeaa)DE-He213
650		4	\|a JAK-STAT inhibitors \|7 (dpeaa)DE-He213
650		4	\|a Ruxolitinib \|7 (dpeaa)DE-He213
650		4	\|a Sarilumab \|7 (dpeaa)DE-He213
650		4	\|a Severe respiratory syndrome \|7 (dpeaa)DE-He213
650		4	\|a Siltuximab \|7 (dpeaa)DE-He213
650		4	\|a Tocilizumab \|7 (dpeaa)DE-He213
700	1		\|a Tsiodras, Sotirios \|e verfasserin \|4 aut
700	1		\|a Tsirigotis, Panagiotis \|e verfasserin \|4 aut
773	0	8	\|i Enthalten in \|t Infectious diseases and therapy \|d Heidelberg : Springer, 2012 \|g 9(2020), 4 vom: 12. Aug., Seite 707-713 \|w (DE-627)735690766 \|w (DE-600)2701611-0 \|x 2193-6382 \|7 nnns
773	1	8	\|g volume:9 \|g year:2020 \|g number:4 \|g day:12 \|g month:08 \|g pages:707-713
856	4	0	\|u https://dx.doi.org/10.1007/s40121-020-00326-1 \|z kostenfrei \|3 Volltext
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_SPRINGER
912			\|a SSG-OLC-PHA
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 9 \|j 2020 \|e 4 \|b 12 \|c 08 \|h 707-713

Indexfelder

author_variant	j m jm s t st p t pt
matchkey_str	article:21936382:2020----::nelui6lcigsasaihbtofrrvninfugnu
hierarchy_sort_str	2020
publishDate	2020
allfields	10.1007/s40121-020-00326-1 doi (DE-627)SPR042044030 (SPR)s40121-020-00326-1-e DE-627 ger DE-627 rakwb eng 610 ASE Meletiadis, Joseph verfasserin aut Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial. COVID-19 (dpeaa)DE-He213 Cytokine storm (dpeaa)DE-He213 IL6 blocking (dpeaa)DE-He213 JAK-STAT inhibitors (dpeaa)DE-He213 Ruxolitinib (dpeaa)DE-He213 Sarilumab (dpeaa)DE-He213 Severe respiratory syndrome (dpeaa)DE-He213 Siltuximab (dpeaa)DE-He213 Tocilizumab (dpeaa)DE-He213 Tsiodras, Sotirios verfasserin aut Tsirigotis, Panagiotis verfasserin aut Enthalten in Infectious diseases and therapy Heidelberg : Springer, 2012 9(2020), 4 vom: 12. Aug., Seite 707-713 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:9 year:2020 number:4 day:12 month:08 pages:707-713 https://dx.doi.org/10.1007/s40121-020-00326-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 4 12 08 707-713
spelling	10.1007/s40121-020-00326-1 doi (DE-627)SPR042044030 (SPR)s40121-020-00326-1-e DE-627 ger DE-627 rakwb eng 610 ASE Meletiadis, Joseph verfasserin aut Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial. COVID-19 (dpeaa)DE-He213 Cytokine storm (dpeaa)DE-He213 IL6 blocking (dpeaa)DE-He213 JAK-STAT inhibitors (dpeaa)DE-He213 Ruxolitinib (dpeaa)DE-He213 Sarilumab (dpeaa)DE-He213 Severe respiratory syndrome (dpeaa)DE-He213 Siltuximab (dpeaa)DE-He213 Tocilizumab (dpeaa)DE-He213 Tsiodras, Sotirios verfasserin aut Tsirigotis, Panagiotis verfasserin aut Enthalten in Infectious diseases and therapy Heidelberg : Springer, 2012 9(2020), 4 vom: 12. Aug., Seite 707-713 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:9 year:2020 number:4 day:12 month:08 pages:707-713 https://dx.doi.org/10.1007/s40121-020-00326-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 4 12 08 707-713
allfields_unstemmed	10.1007/s40121-020-00326-1 doi (DE-627)SPR042044030 (SPR)s40121-020-00326-1-e DE-627 ger DE-627 rakwb eng 610 ASE Meletiadis, Joseph verfasserin aut Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial. COVID-19 (dpeaa)DE-He213 Cytokine storm (dpeaa)DE-He213 IL6 blocking (dpeaa)DE-He213 JAK-STAT inhibitors (dpeaa)DE-He213 Ruxolitinib (dpeaa)DE-He213 Sarilumab (dpeaa)DE-He213 Severe respiratory syndrome (dpeaa)DE-He213 Siltuximab (dpeaa)DE-He213 Tocilizumab (dpeaa)DE-He213 Tsiodras, Sotirios verfasserin aut Tsirigotis, Panagiotis verfasserin aut Enthalten in Infectious diseases and therapy Heidelberg : Springer, 2012 9(2020), 4 vom: 12. Aug., Seite 707-713 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:9 year:2020 number:4 day:12 month:08 pages:707-713 https://dx.doi.org/10.1007/s40121-020-00326-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 4 12 08 707-713
allfieldsGer	10.1007/s40121-020-00326-1 doi (DE-627)SPR042044030 (SPR)s40121-020-00326-1-e DE-627 ger DE-627 rakwb eng 610 ASE Meletiadis, Joseph verfasserin aut Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial. COVID-19 (dpeaa)DE-He213 Cytokine storm (dpeaa)DE-He213 IL6 blocking (dpeaa)DE-He213 JAK-STAT inhibitors (dpeaa)DE-He213 Ruxolitinib (dpeaa)DE-He213 Sarilumab (dpeaa)DE-He213 Severe respiratory syndrome (dpeaa)DE-He213 Siltuximab (dpeaa)DE-He213 Tocilizumab (dpeaa)DE-He213 Tsiodras, Sotirios verfasserin aut Tsirigotis, Panagiotis verfasserin aut Enthalten in Infectious diseases and therapy Heidelberg : Springer, 2012 9(2020), 4 vom: 12. Aug., Seite 707-713 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:9 year:2020 number:4 day:12 month:08 pages:707-713 https://dx.doi.org/10.1007/s40121-020-00326-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 4 12 08 707-713
allfieldsSound	10.1007/s40121-020-00326-1 doi (DE-627)SPR042044030 (SPR)s40121-020-00326-1-e DE-627 ger DE-627 rakwb eng 610 ASE Meletiadis, Joseph verfasserin aut Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial. COVID-19 (dpeaa)DE-He213 Cytokine storm (dpeaa)DE-He213 IL6 blocking (dpeaa)DE-He213 JAK-STAT inhibitors (dpeaa)DE-He213 Ruxolitinib (dpeaa)DE-He213 Sarilumab (dpeaa)DE-He213 Severe respiratory syndrome (dpeaa)DE-He213 Siltuximab (dpeaa)DE-He213 Tocilizumab (dpeaa)DE-He213 Tsiodras, Sotirios verfasserin aut Tsirigotis, Panagiotis verfasserin aut Enthalten in Infectious diseases and therapy Heidelberg : Springer, 2012 9(2020), 4 vom: 12. Aug., Seite 707-713 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:9 year:2020 number:4 day:12 month:08 pages:707-713 https://dx.doi.org/10.1007/s40121-020-00326-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2020 4 12 08 707-713
language	English
source	Enthalten in Infectious diseases and therapy 9(2020), 4 vom: 12. Aug., Seite 707-713 volume:9 year:2020 number:4 day:12 month:08 pages:707-713
sourceStr	Enthalten in Infectious diseases and therapy 9(2020), 4 vom: 12. Aug., Seite 707-713 volume:9 year:2020 number:4 day:12 month:08 pages:707-713
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	COVID-19 Cytokine storm IL6 blocking JAK-STAT inhibitors Ruxolitinib Sarilumab Severe respiratory syndrome Siltuximab Tocilizumab
dewey-raw	610
isfreeaccess_bool	true
container_title	Infectious diseases and therapy
authorswithroles_txt_mv	Meletiadis, Joseph @@aut@@ Tsiodras, Sotirios @@aut@@ Tsirigotis, Panagiotis @@aut@@
publishDateDaySort_date	2020-08-12T00:00:00Z
hierarchy_top_id	735690766
dewey-sort	3610
id	SPR042044030
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR042044030</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519234052.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201122s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s40121-020-00326-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR042044030</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s40121-020-00326-1-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Meletiadis, Joseph</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">COVID-19</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cytokine storm</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IL6 blocking</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">JAK-STAT inhibitors</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ruxolitinib</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Sarilumab</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Severe respiratory syndrome</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Siltuximab</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tocilizumab</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tsiodras, Sotirios</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tsirigotis, Panagiotis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Infectious diseases and therapy</subfield><subfield code="d">Heidelberg : Springer, 2012</subfield><subfield code="g">9(2020), 4 vom: 12. Aug., Seite 707-713</subfield><subfield code="w">(DE-627)735690766</subfield><subfield code="w">(DE-600)2701611-0</subfield><subfield code="x">2193-6382</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:9</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:4</subfield><subfield code="g">day:12</subfield><subfield code="g">month:08</subfield><subfield code="g">pages:707-713</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1007/s40121-020-00326-1</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">9</subfield><subfield code="j">2020</subfield><subfield code="e">4</subfield><subfield code="b">12</subfield><subfield code="c">08</subfield><subfield code="h">707-713</subfield></datafield></record></collection>
author	Meletiadis, Joseph
spellingShingle	Meletiadis, Joseph ddc 610 misc COVID-19 misc Cytokine storm misc IL6 blocking misc JAK-STAT inhibitors misc Ruxolitinib misc Sarilumab misc Severe respiratory syndrome misc Siltuximab misc Tocilizumab Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19
authorStr	Meletiadis, Joseph
ppnlink_with_tag_str_mv	@@773@@(DE-627)735690766
format	electronic Article
dewey-ones	610 - Medicine & health
delete_txt_mv	keep
author_role	aut aut aut
collection	springer
remote_str	true
illustrated	Not Illustrated
issn	2193-6382
topic_title	610 ASE Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19 COVID-19 (dpeaa)DE-He213 Cytokine storm (dpeaa)DE-He213 IL6 blocking (dpeaa)DE-He213 JAK-STAT inhibitors (dpeaa)DE-He213 Ruxolitinib (dpeaa)DE-He213 Sarilumab (dpeaa)DE-He213 Severe respiratory syndrome (dpeaa)DE-He213 Siltuximab (dpeaa)DE-He213 Tocilizumab (dpeaa)DE-He213
topic	ddc 610 misc COVID-19 misc Cytokine storm misc IL6 blocking misc JAK-STAT inhibitors misc Ruxolitinib misc Sarilumab misc Severe respiratory syndrome misc Siltuximab misc Tocilizumab
topic_unstemmed	ddc 610 misc COVID-19 misc Cytokine storm misc IL6 blocking misc JAK-STAT inhibitors misc Ruxolitinib misc Sarilumab misc Severe respiratory syndrome misc Siltuximab misc Tocilizumab
topic_browse	ddc 610 misc COVID-19 misc Cytokine storm misc IL6 blocking misc JAK-STAT inhibitors misc Ruxolitinib misc Sarilumab misc Severe respiratory syndrome misc Siltuximab misc Tocilizumab
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	Infectious diseases and therapy
hierarchy_parent_id	735690766
dewey-tens	610 - Medicine & health
hierarchy_top_title	Infectious diseases and therapy
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)735690766 (DE-600)2701611-0
title	Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19
ctrlnum	(DE-627)SPR042044030 (SPR)s40121-020-00326-1-e
title_full	Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19
author_sort	Meletiadis, Joseph
journal	Infectious diseases and therapy
journalStr	Infectious diseases and therapy
lang_code	eng
isOA_bool	true
dewey-hundreds	600 - Technology
recordtype	marc
publishDateSort	2020
contenttype_str_mv	txt
container_start_page	707
author_browse	Meletiadis, Joseph Tsiodras, Sotirios Tsirigotis, Panagiotis
container_volume	9
class	610 ASE
format_se	Elektronische Aufsätze
author-letter	Meletiadis, Joseph
doi_str_mv	10.1007/s40121-020-00326-1
dewey-full	610
author2-role	verfasserin
title_sort	interleukin-6 blocking vs. jak-stat inhibition for prevention of lung injury in patients with covid-19
title_auth	Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19
abstract	Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial.
abstractGer	Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial.
abstract_unstemmed	Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
container_issue	4
title_short	Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19
url	https://dx.doi.org/10.1007/s40121-020-00326-1
remote_bool	true
author2	Tsiodras, Sotirios Tsirigotis, Panagiotis
author2Str	Tsiodras, Sotirios Tsirigotis, Panagiotis
ppnlink	735690766
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.1007/s40121-020-00326-1
up_date	2024-07-04T00:35:03.059Z
_version_	1803606612310491136
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR042044030</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519234052.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201122s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s40121-020-00326-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR042044030</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s40121-020-00326-1-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Meletiadis, Joseph</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract The severe respiratory insufficiency observed during COVID-19 infection may not be directly related to a cytopathogenic effect induced by the virus itself, but to an exaggerated and inappropriate immune response. In an effort to reduce the severity of organ dysfunction, including respiratory insufficiency, monoclonal antibodies (Mabs) that block the interleukin-6 receptor, such as tocilizumab, sarilumab, and siltuximab, are under investigation for the treatment of COVID-19. However, blocking of just one of the many cytokines involved in the inflammatory reaction may not slow down the magnitude of the process. Since timing is important, the immune deficiency induced by IL6 blockade at the late immunodeficiency phase of sepsis that follows the initial inflammatory response may be detrimental. Finally, monitoring the degree and duration of IL6 blockade may be challenging because of the long half-life of Mabs (2–3 weeks). Pro- and anti-inflammatory cytokines act through a common JAK-STAT signaling pathway, which can be inhibited by JAK-STAT inhibitors. Ruxolitinib, a tyrosine kinase inhibitor selective for JAK1, 2, blocks many pro- and anti-inflammatory cytokines including IL6. Ruxolitinib has favorable pharmacodynamics and an acceptable safety profile. The short half-life (4–6 h) of the drug offers the opportunity for ideal monitoring of the degree and duration of cytokine blocking, simply by the adjusting dose and duration of therapy. From a theoretical point of view, the balanced control of cytokine blockade throughout the course of the septic process should be the cornerstone of modern management. According to this hypothesis, maximization of blocking should be attempted at the phase of hyper-inflammation for preventing severe organ damage, while pro-inflammatory blockade should be minimized at the late phase of immunoparalysis for prevention of secondary infections. Based on the above considerations, we consider that the efficacy and safety of this drug deserves testing in the context of a controlled randomized trial.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">COVID-19</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cytokine storm</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IL6 blocking</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">JAK-STAT inhibitors</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ruxolitinib</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Sarilumab</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Severe respiratory syndrome</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Siltuximab</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tocilizumab</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tsiodras, Sotirios</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tsirigotis, Panagiotis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Infectious diseases and therapy</subfield><subfield code="d">Heidelberg : Springer, 2012</subfield><subfield code="g">9(2020), 4 vom: 12. Aug., Seite 707-713</subfield><subfield code="w">(DE-627)735690766</subfield><subfield code="w">(DE-600)2701611-0</subfield><subfield code="x">2193-6382</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:9</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:4</subfield><subfield code="g">day:12</subfield><subfield code="g">month:08</subfield><subfield code="g">pages:707-713</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1007/s40121-020-00326-1</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">9</subfield><subfield code="j">2020</subfield><subfield code="e">4</subfield><subfield code="b">12</subfield><subfield code="c">08</subfield><subfield code="h">707-713</subfield></datafield></record></collection>
score	7.3996468

Nicht das Richtige dabei?

Schreiben Sie uns!

Interleukin-6 Blocking vs. JAK-STAT Inhibition for Prevention of Lung Injury in Patients with COVID-19

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?