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.