The role of interleukin-1 family members in hyperuricemia and gout
SourceJoint Bone Spine, 88, 2, (2021), article 105092
Article / Letter to editor
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Joint Bone Spine
SubjectRadboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 5: Inflammatory diseases RIMLS: Radboud Institute for Molecular Life Sciences
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-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. FINDINGS: 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. 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.
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