Open Access

REVIEW

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

Diana Boraschi¹, Davide Lucchesi¹, Stefan Hainzl², Maria Leitner², Elisabeth Maier², Doris Mangelberger², Gertie J. Oostingh², Tobias Pfaller², Claudia Pixner², Gernot Posselt², Paola Italiani¹, Marcel F. Nold^3,4, Claudia A. Nold-Petry^3,4, Philip Bufler⁵, Charles A. Dinarello³

1 Laboratory of Innate Immunity and Cytokines, Institute of Biomedical Technologies, National Research Council, I-56124 Pisa, Italy
2 Department of Molecular Biology, University of Salzburg, Austria
3 Department of Medicine, University of Colorado Denver, Aurora, CO, USA
4 The Ritchie Centre, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia
5 Children’s Hospital, Ludwig-Maximilians University, Munich, Germany

European Cytokine Network 2011, 22(3), 127-47. https://doi.org/10.1684/ecn.2011.0288

Accepted 07 August 2011;

Abstract

The IL-1 family of cytokines encompasses eleven proteins that each share a similar β-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-1α (IL-1F1), IL-1β (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 α 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-1α and IL-33, for receptor-independent organ/tissue-specific regulation of inflammation is also reviewed.

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