Rethinking interleukin-6 blockade for treatment of COVID-19

S Scherger, A Henao-Martínez, C Franco-Paredes, L Shapiro, S Scherger, A Henao-Martínez, C Franco-Paredes, L Shapiro

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine with effects in immune regulation, inflammation, and infection. The use of drugs that inhibit IL-6 biological activity has been proposed as a treatment for patients with Coronavirus Disease 2019 (COVID-19). The rationale for this approach includes commitment to the concept that inflammation is a cause of lung damage in COVID-19 and belief that IL-6 is a pro-inflammatory molecule. Observational data thought to support IL-6 inhibition include elevated circulating IL-6 levels in COVID-19 patients and association between elevated IL-6 and poor clinical outcomes. However, IL-6 has significant anti-inflammatory properties, which calls into question the rationale for employing IL-6 blockade to suppress inflammation-induced tissue injury. Also, studies suggesting a beneficial role for IL-6 in the host response to infection challenge the strategy of using IL-6 blockade to treat COVID-19. In studies of recombinant IL-6 injected into human volunteers, IL-6 levels exceeding those measured in COVID-19 patients have been observed with no pulmonary adverse events or other organ damage. These observations question the role of IL-6 as a contributing factor in COVID-19. Clinical experience with IL-6 receptor antagonists such as tocilizumab demonstrates increase in severe and opportunistic infections, raising concern about using tocilizumab and similar agents to treat COVID-19. Trials of drugs to inhibit IL-6 activity in COVID-19 are ongoing and will shed light on the role of IL-6 in COVID-19 pathogenesis. However, until more information is available, providers should exercise caution in prescribing these therapies given the potential for patient harm.

Keywords: COVID-19; IL-6; IL-6 blockade; IL-6 inhibitors; IL-6 receptor antagonists; SARS-CoV-2; Tocilizumab.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

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