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

Viola Klück,Ruiqi Liu,Leo A.B Joosten

doi:10.1016/j.jbspin.2020.105092

Abstract

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-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β and IL-36γ are considered pro-inflammatory and IL-1Ra, IL-36Ra, IL-37 and IL-38 anti-inflammatory. Whereas IL-1β 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. Studies indicate IL-1α, like IL-1β, 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-1β blockers, several new therapeutics to treat gout are being developed either inhibiting the transcription or maturation of IL-1β. Inthis 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.

Highlights

Introduction interleukin1 family membersThe interleukin (IL)-1 family consists of 11 members containing the IL-1 consensus sequence A-X-D, where A is an aliphatic amino acid, X is any amino acid and D is aspartic acid
Pro-inflammatory members bind to their receptors which dimerize with a co-receptor through their TIR domains, recruiting the TIR domain-containing adaptor protein MyD88 to activate IL-1R-associate kinases (IRAKs)
IL-1␤ plays a pivotal role in gout, though increasing evidence suggests other IL-1 family members are involved in gout

Summary

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-1␣, IL-1␤, IL-18, IL-33, IL-36␣, IL-36␤ and IL-36␥ are considered pro-inflammatory and IL-1Ra, IL-36Ra, IL-37 and IL-38 antiinflammatory. Whereas IL-1␤ has a known pivotal role in gout, increasing evidence suggests other IL-1 family members are involved in the pathogenesis of hyperuricemia and gout flares. IL-18, 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. IL-1Ra, IL-33, IL-37 and IL-38 inhibit MSU crystal-induced inflammation and have therapeutic potential for treatment of gout flares. Conclusion: In this review, IL-1 family cytokines are discussed in the context of hyperuricemia and gout. Current and novel therapeutic options for targeting IL-1 are reviewed

Introduction interleukin-1 family members

Anti-IL-1 treatment for gout

Findings

Summary and future directions