The role of IL-6 and IL-6 blockade in COVID-19

Expert Rev Clin Immunol. 2021 Jun;17(6):601-618. doi: 10.1080/1744666X.2021.1919086. Epub 2021 May 27.

Abstract

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a dysregulated hyperinflammatory response.

Areas covered: Authors review evidence on IL-6 and IL-6 blockade in coronavirus disease 2019 (COVID-19) and discuss the pathophysiological and prognostic roles of this cytokine and the clinical impact of pharmacological blockade of IL-6 . The material includes original articles and reviews published from March 2020 to March 2021 and searched on PubMed, medRxiv, and bioRxiv.

Expert opinion: IL-6 is one of the most prominent pro-inflammatory cytokines. Increased levels are recorded in COVID-19 patients, especially those with severe-to-critical disease. Evidence is accumulating on the relevance of IL-6 as a prognostic marker in COVID-19. Since IL-6 is a druggable target for several inflammatory diseases, pharmacological blockers of the IL-6 signaling pathway were repurposed to blunt the abnormal SARS-CoV-2-induced cytokine release. Data are limited to few randomized controlled trials that reported encouraging, though not conclusive, results, indicating the usefulness of IL-6 blockade early in the course of the disease in patients with hyperinflammation and no or limited organ damage. Further research is warranted to explore the role of IL-6 in different COVID-19 phenotypes and identify subgroups of patients who may mostly benefit from IL-6 pathway inhibition.

Keywords: COVID-19; IL-6; SARS-CoV-2; cytokine storm; hyperinflammation; lymphocytes; pathophysiology; prognosis; sarilumab; siltuximab; tocilizumab.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • COVID-19 / immunology
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Host-Pathogen Interactions
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / metabolism
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / metabolism
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • Signal Transduction
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Interleukin-6
  • Receptors, Interleukin-6