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Rethinking interleukin-6 blockade for treatment of COVID-19.

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  • 1Division of Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora CO 80045, United States.

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Summary

Interleukin-6 (IL-6) has complex roles in inflammation and infection. Blocking IL-6 for COVID-19 treatment is questionable due to its anti-inflammatory functions and potential for increased infections.

Keywords:
COVID-19IL-6IL-6 blockadeIL-6 inhibitorsIL-6 receptor antagonistsSARS-CoV-2Tocilizumab

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Area of Science:

  • Immunology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Interleukin-6 (IL-6) is a cytokine involved in immune regulation, inflammation, and infection.
  • IL-6 inhibition has been proposed for treating Coronavirus Disease 2019 (COVID-19) due to its perceived pro-inflammatory role and association with poor outcomes.
  • Elevated IL-6 levels are observed in COVID-19 patients, supporting the rationale for IL-6 blockade.

Purpose of the Study:

  • To critically evaluate the rationale for using IL-6 inhibitors in COVID-19 treatment.
  • To examine the dual role of IL-6 in inflammation and host defense.
  • To assess the safety and efficacy concerns associated with IL-6 blockade in the context of COVID-19.

Main Methods:

  • Review of existing literature on IL-6 function, COVID-19 pathogenesis, and clinical trial data.
  • Analysis of observational data linking IL-6 levels to COVID-19 severity.
  • Consideration of studies involving recombinant IL-6 administration and clinical experience with IL-6 receptor antagonists.

Main Results:

  • IL-6 exhibits significant anti-inflammatory properties, challenging its role as a solely pro-inflammatory mediator in COVID-19.
  • Studies indicate IL-6 plays a beneficial role in host response to infection.
  • Recombinant IL-6 administration at levels exceeding those in COVID-19 patients did not cause pulmonary or organ damage.
  • Clinical use of IL-6 receptor antagonists has been associated with increased severe and opportunistic infections.

Conclusions:

  • The rationale for IL-6 blockade in COVID-19 is questionable given IL-6's anti-inflammatory functions and potential benefits in host defense.
  • Clinical data raises concerns about increased infection risk with IL-6 receptor antagonists.
  • Caution is advised when prescribing IL-6 inhibitors for COVID-19 until further clinical trial data clarifies their role and safety.