The role of interleukin-1 family members in hyperuricemia and gout

Background: Interleukin (IL)-1 family cytokines and their receptors have important roles in innate and partly in adaptive immunity. The family consists of 11 members of which IL-1a, IL-1p, IL-18, IL-33, IL-36a, IL-36p and IL-36y are considered pro-inflammatory and IL-1Ra, IL-36Ra, IL-37 and IL-38 antiinflammatory. Whereas IL-1p has a known pivotal role in gout, increasing evidence suggests other IL-1 family members are also involved in the pathogenesis of hyperuricemia and gout flares. Findings: Studies indicate IL-1a, like IL-1p, plays an essential role in the pathogenesis of gout flares. IL-18, although elevated in patients with gout, does not contribute to MSU crystal-induced inflammation, but may be involved in the subsequent development of cardiovascular disease in individuals with gout. The role of the pro-inflammatory cytokine IL-36 in gout remains elusive. In contrast, IL-1Ra, IL-33, IL-37 and IL-38 inhibit MSU crystal-induced inflammation and therefore have therapeutic potential for treatment of gout flares. In addition to existing IL-1p blockers, several new therapeutics to treat gout are being developed either inhibiting the transcription or maturation of IL-1p. Conclusion: In this review, IL-1 family cytokines are discussed in the context of hyperuricemia and gout. Finally, current and novel therapeutic options for targeting IL-1 are reviewed. (C) 2020 The Authors. Published by Elsevier Masson SAS on behalf of Societe francaise de rhumatologie. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

The study discusses the roles of IL-1 family cytokines in hyperuricemia and gout, highlighting the importance of IL-1a and IL-1β in gout flares, while other members such as IL-18, IL-33, IL-37, and IL-38 show therapeutic potential for gout flares. New therapeutics targeting IL-1 are also being developed for the treatment of gout.