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Rethinking interleukin-6 blockade for treatment of COVID-19.
Med Hypotheses. 2020 Jun 27; 144:110053.MH

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.

Authors+Show Affiliations

Division of Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora CO 80045, United States. Electronic address: sias.scherger@cuanschutz.edu.Division of Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora CO 80045, United States.Division of Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora CO 80045, United States; Hospital Infantil de México, Federico Gómez, México City, México.Division of Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora CO 80045, United States; Division of Infectious Diseases, Rocky Mountain Regional Veterans Affairs Medical Center, 1700 N Wheeling St, Aurora, CO 80045, United States; Supported by The Emily Foundation for Medical Research, One Beacon Street, 15th Floor, Boston MA 02108, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32758889

Citation

Scherger, S, et al. "Rethinking Interleukin-6 Blockade for Treatment of COVID-19." Medical Hypotheses, vol. 144, 2020, p. 110053.
Scherger S, Henao-Martínez A, Franco-Paredes C, et al. Rethinking interleukin-6 blockade for treatment of COVID-19. Med Hypotheses. 2020;144:110053.
Scherger, S., Henao-Martínez, A., Franco-Paredes, C., & Shapiro, L. (2020). Rethinking interleukin-6 blockade for treatment of COVID-19. Medical Hypotheses, 144, 110053. https://doi.org/10.1016/j.mehy.2020.110053
Scherger S, et al. Rethinking Interleukin-6 Blockade for Treatment of COVID-19. Med Hypotheses. 2020 Jun 27;144:110053. PubMed PMID: 32758889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rethinking interleukin-6 blockade for treatment of COVID-19. AU - Scherger,S, AU - Henao-Martínez,A, AU - Franco-Paredes,C, AU - Shapiro,L, Y1 - 2020/06/27/ PY - 2020/05/01/received PY - 2020/06/24/revised PY - 2020/06/25/accepted PY - 2020/8/8/entrez PY - 2020/8/8/pubmed PY - 2020/8/8/medline KW - COVID-19 KW - IL-6 KW - IL-6 blockade KW - IL-6 inhibitors KW - IL-6 receptor antagonists KW - SARS-CoV-2 KW - Tocilizumab SP - 110053 EP - 110053 JF - Medical hypotheses JO - Med. Hypotheses VL - 144 N2 - 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. SN - 1532-2777 UR - https://www.unboundmedicine.com/medline/citation/32758889/Rethinking_interleukin-6_blockade_for_treatment_of_COVID-19 L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(20)31065-3 DB - PRIME DP - Unbound Medicine ER -
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