In acute gout, interleukin-1β plays a central role in the inflammatory cascade triggered by monosodium urate (MSU) crystals. Which mechanism activates IL-1β in gout?

• A MSU crystals directly activate TLR-2 and TLR-4 on macrophages, releasing pre-formed IL-1β
• B MSU crystals are phagocytosed by macrophages and activate the NLRP3 inflammasome, converting pro-IL-1β to active IL-1β via caspase-1 ✓
• C Uric acid in solution activates complement C3 convertase, which cleaves IL-1β
• D MSU crystals trigger NF-κB via RAGE receptor, leading to IL-6 which then cleaves IL-1β

Explanation

MSU crystals are recognised as a danger signal (DAMP) by NLRP3 inflammasome components within macrophage cytoplasm after phagocytosis. Crystal-mediated lysosomal rupture and reactive oxygen species activate NLRP3, which oligomerises with ASC adapter protein, recruits and activates caspase-1, which then cleaves pro-IL-1β to biologically active IL-1β. This is why anakinra (IL-1Ra) and canakinumab (anti-IL-1β) are effective treatments for gout flares refractory to colchicine or NSAIDs. This mechanism also explains why colchicine inhibits neutrophil microtubule-dependent IL-1β secretion rather than inflammasome assembly per se.

Reference: Maheshwari Essential Orthopaedics, 6th ed.

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