Immunometabolic regulation in gouty arthritis: current evidence, mechanistic insights, and remaining challenges.

Gouty arthritis is driven by monosodium urate (MSU) crystal deposition and acute activation of the NLRP3 inflammasome-IL-1β axis. However, crystal burden alone does not fully explain asymptomatic crystal deposition, recurrent flares, or the self-limiting nature of acute inflammation. Immunometabolism provides a useful perspective for understanding these differences. In macrophages, glycolysis supports pro-IL-1β expression and inflammatory mediator production, while tricarboxylic acid cycle remodeling, mitochondrial stress, and reactive oxygen species may contribute to inflammasome activation. In neutrophils, glycolysis sustains rapid effector functions, including chemotaxis, degranulation, ROS production, and neutrophil extracellular trap formation. During later stages, efferocytosis, lipid mediator switching, and mitochondrial adaptation may promote inflammation resolution. Systemic metabolic abnormalities may further influence recurrence susceptibility by altering innate immune responsiveness to MSU crystals. This review summarizes current evidence linking immunometabolic pathways to gouty inflammation and discusses remaining questions regarding cell specificity, temporal sequence, causal relevance, and therapeutic translation.