Suppression of innate inflammation and immunity by interleukin-37

Charles A Dinarello, Claudia Nold-Petry, Marcel Nold, Mayumi Fujita, Suzhao Li, Soohyun Kim, Philip Bufler

Research output: Contribution to journalArticleResearchpeer-review

182 Citations (Scopus)


IL-37 is unique in the IL-1 family in that unlike other members of the family, IL-37 broadly suppresses innate immunity. IL-37 can be elevated in humans with inflammatory and autoimmune diseases where it likely functions to limit inflammation. Transgenic mice expressing human IL-37 (IL37-tg) exhibit less severe inflammation in models of endotoxin shock, colitis, myocardial infarction, lung, and spinal cord injury. IL37-tg mice have reduced antigen-specific responses and dendritic cells (DCs) from these mice exhibit characteristics of tolerogenic DCs. Compared to aging wild-type (WT) mice, aging IL37-tg mice are protected against B-cell leukemogenesis and heart failure. Treatment of WT mice with recombinant human IL-37 has been shown to be protective in several models of inflammation and injury. IL-37 binds to the IL-18 receptor but then recruits the orphan IL-1R8 (formerly TIR8 or SIGIRR) in order to function as an inhibitor. Here, we review the discovery of IL-37, its production, release, and mechanisms by which IL-37 reduces inflammation and suppresses immune responses. The data reviewed here suggest a therapeutic potential for IL-37.

Original languageEnglish
Pages (from-to)1067-1081
Number of pages15
JournalEuropean Journal of Immunology
Issue number5
Publication statusPublished - 1 May 2016


  • Autoinflammation
  • Caspase-1
  • IL-1 family
  • Toll receptors

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