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 respirator...
Ausführliche Beschreibung
Autor*in: |
Meletiadis, Joseph [verfasserIn] Tsiodras, Sotirios [verfasserIn] Tsirigotis, Panagiotis [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Übergeordnetes Werk: |
Enthalten in: Infectious diseases and therapy - Heidelberg : Springer, 2012, 9(2020), 4 vom: 12. Aug., Seite 707-713 |
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Übergeordnetes Werk: |
volume:9 ; year:2020 ; number:4 ; day:12 ; month:08 ; pages:707-713 |
Links: |
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DOI / URN: |
10.1007/s40121-020-00326-1 |
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Katalog-ID: |
SPR042044030 |
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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. | ||
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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 |
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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 |
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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 |
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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 |
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isOA_txt |
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hochschulschrift_bool |
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doi_str |
10.1007/s40121-020-00326-1 |
up_date |
2024-07-04T00:35:03.059Z |
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1803606612310491136 |
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