Our data indicate that MSU may activate TLR4, SYK, iNOS and TRPV1 to induce the release of IL-1β by macrophages, triggering nociception and inflammation during acute gout attack.
More importantly, it is proposed that the inhibiting of glycolysis pathway would be a new avenue for the treatment of gout flare and other IL-1β related diseases.
Anti-inflammatory agents, such corticosteroids, NSAIDs and colchicine, are widely used for the treatment of gout flare; recognition of the importance of NLRP3 inflammasome activation and bioactive IL-1β release in initiation of the gout flare has led to the development of anti-IL-1β biological therapy for gout flares.
Several recent studies have demonstrated a significant decrease of serum urate during acute gout attack, which is an aseptic inflammation process focusing on IL-1β.
The expressions of PYCARD gene transcript variant mRNA and interleukin-1β (IL-1β) mRNA in PBMCs were investigated in 96 PG patients with acute phase (APPG, 44 cases) and non-acute phase (NAPPG, 52 cases) and 30 healthy controls (HCs) by reverse transcription-polymerase chain reaction (PCR) and/or realtime quantitative PCR.
The translation of our knowledge of the biology of MSU crystal-induced IL-1 secretion gives rise to new targets and therapeutic strategies in the treatment of acute gout.
However, some hyperuricemia patients, even gouty patients with tophi in the joints, never experience gout attack, which indicates that pathogenic pathways other than MSU participate in the secretion of IL-1β in the pathogenesis of acute gouty arthritis.
Altogether, macrophage migration inhibitory factor promotes neutrophil accumulation and is important for IL-1β production, which are 2 crucial events contributing to the pathogenesis of acute gout.
IL-1β is a central cytokine in the initiation of the acute inflammatory response, which plays a key role in the pathogenesis of gout and the pathology of acute gouty arthritis.
Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis.
Canakinumab (Ilaris®), an anti-interleukin-1β monoclonal antibody, is a novel approach to treat acute gouty arthritis flares in a targeted population of patients in whom treatment options are limited.
Anti-inflammatory agents, such corticosteroids, NSAIDs and colchicine, are widely used for the treatment of gout flare; recognition of the importance of NLRP3 inflammasome activation and bioactive IL-1β release in initiation of the gout flare has led to the development of anti-IL-1β biological therapy for gout flares.
We also summarized the potential use of phytochemicals on NLRP3 inflammasome-mediated diseases, suggesting that phytochemicals can further prevent acute gout attack.
Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis.
The central role of NALP3 inflammasome activation and IL-1beta signalling in the initiation of the acute gout attack raises the possibility of new therapeutic targets.
Our data indicate that MSU may activate TLR4, SYK, iNOS and TRPV1 to induce the release of IL-1β by macrophages, triggering nociception and inflammation during acute gout attack.
The translation of our knowledge of the biology of MSU crystal-induced IL-1 secretion gives rise to new targets and therapeutic strategies in the treatment of acute gout.
This study showed that DNI was an effective independent marker to differentiate between an acute gout attack and cellulitis at the crucial early phase irrespective of MSU crystal confirmation or serum uric acid concentration.