Monosodium urate-induced inflammation plays a vital role in acute gout (AG). Inflammation is a multi-stage process involved in the acute release of arachidonic acid and its metabolites. However, the function of the metabolism of arachidonic acid and other polyunsaturated fatty acids in AG is not well understood. This study aimed to investigate the modification of polyunsaturated fatty acid metabolism by AG.

Plasma samples from patients with an AG attack (n = 26) and gender-matched healthy controls (n = 26) were analysed by metabolic profiling of polyunsaturated fatty acids. The findings were further validated with a second cohort (n = 20 each group). The associated mechanisms were investigated in whole blood cells from the second cohort and neutrophils in vitro.

Plasma metabolic profiling revealed a significant increase in leukotriene B₄ (LTB₄) for AG patients in both cohorts. The increase in plasma LTB₄ was accounted for by the dynamic balance between the activation of 5-lipoxygenase and CYP4F3, the former mediating the biosynthesis of LTB₄ and the latter mediating its metabolism. This was supported by significantly increased transcriptional levels of 5-lipoxygenase and CYP4F3 in whole blood cells from AG patients compared with those of controls, and the uric acid-caused dose-relevant and time-dependent activation of 5-lipoxygenase and CYP4F3 at the transcriptional and molecular levels in vitro.

Increased LTB₄ in AG patients is mainly due to activation of 5-lipoxygenase. 5-Lipoxygenase inhibition may be of therapeutic value clinically.