Circulating hydroxy fatty acids in I (neutrophil aggregation/lipoxygenase/icosanoids/colchicine)

Episodes of fever, serositis, and arthritis in familial Mediterranean fever (FMF) suggested circulating me- diators of acute inflammation (e.g., neutrophil activation). The mean serum neutrophil-aggregating activity of 51 FMF patients was 2.5 ? 0.2 cm2/min, compared to 1.0 ? 0.1 cm2/min in 20 normal controls (P < 0.0002). Lipid extracts of FMF sera retained neutrophil-aggregating activity and had UV absorbance peaks at 269 and 279 nm, indicating the pres- ence of lipids with a conjugated triene structure. Chromatog- raphy of extracts yielded peaks that were coeluted with refer- ence dihydroxyicosatetraenoic acids, had UV absorbance peaks at 259, 269, and 279 nm, and possessed neutrophil-ag- gregating activity. The presence of leukotriene B4 was exclud- ed by chromatography following methyl-esterification. Monohydroxy compounds identified in FMF extracts by gas chromatography/mass spectrometry included 5-hydroxyicosa- tetraenoic acid, and 9- and 13-hydroxyoctadecadienoic acids. Hydroxy acids were present in 19 of 31 FMF sera and absent in extracts of sera from 8 patients with active systemic lupus ery- thematosus, 7 with fever from infection, and 12 normal con- trols. The finding of circulating mono- and dihydroxy fatty acids in FMF suggests that defects in the formation or elimina- tion of these compounds might play a role in the pathogenesis of FMF.