title: Suppression of innate inflammation and immunity by interleukin-37.
abstract: 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.
authors.affiliation: University of Colorado Denver, Aurora, CO, USA.|Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Monash University, Melbourne, Australia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nold-Petry
authors.affiliation: Monash University, Melbourne, Australia.
authors.forename: Marcel
authors.initials: M
authors.lastname: Nold
authors.affiliation: University of Colorado Denver, Aurora, CO, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Fujita
authors.affiliation: University of Colorado Denver, Aurora, CO, USA.
authors.forename: Suzhao
authors.initials: S
authors.lastname: Li
authors.affiliation: University of Colorado Denver, Aurora, CO, USA.|Konkuk University, Seoul, Republic of Korea.
authors.forename: Soohyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Ludwig-Maximilian-University, Munich, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Bufler
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D017472:Receptors, Interleukin-1 / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: C508587:IL37 protein, human; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D020170:Caspase 1
keywords: Autoinflammation; Caspase-1; IL-1 family; Toll receptors