IL-37: a new anti-inflammatory cytokine of the IL-1 family

Diana Boraschi, Davide Lucchesi, Stefan Hainzl, Maria Leitner, Elisabeth Maier, Doris Mangelberger, Gertie Oostingh, Tobias Pfaller, Claudia Pixner, Gernot Posselt, Paola Italiani, Marcel Nold, Claudia Nold, Philip Bufler, Charles Dinarello

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231 Citations (Scopus)

Abstract

The IL-1 family of cytokines encompasses eleven proteins that each share a similar beta-barrel structure and bind to Ig-like receptors. Some of the IL-1-like cytokines have been well characterised, and play key roles in the development and regulation of inflammation. Indeed, IL-1alpha (IL-1F1), IL-1beta (IL-1F2), and IL-18 (IL-1F4) are well-known inflammatory cytokines active in the initiation of the inflammatory reaction and in driving Th1 and Th17 inflammatory responses. In contrast, IL-1 receptor antagonist (IL-1Ra, IL-1F3) and the receptor antagonist binding to IL-1Rrp2 (IL-36Ra, IL-1F5) reduce inflammation by blocking the binding of the agonist receptor ligands. In the case of IL-37 (IL-1F7), of which five different splice variants have been described, less is known of its function, and identification of the components of a heterodimeric receptor complex remains unclear. Some studies suggest that IL-37 binds to the alpha chain of the IL-18 receptor in a non-competitive fashion, and this may explain some of the disparate biological effects that have been reported for mice deficient in the IL-18R. The biological properties of IL-37 are mainly those of down-regulating inflammation, as assessed in models where human IL-37 is expressed in mice. In this review, an overview of the role of IL-37 in the regulation of inflammation is presented. The finding that IL-37 also locates to the nucleus, as do IL-1alpha and IL-33, for receptor-independent organ/tissue-specific regulation of inflammation is also reviewed.
Original languageEnglish
Pages (from-to)127 - 147
Number of pages21
JournalEuropean Cytokine Network
Volume22
Issue number3
DOIs
Publication statusPublished - 2011

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