Neutrophil functional and arachidonic acid metabolic correlates and clinical disease activity in pirazolac-treated rheumatoid arthritis patients

Neutrophils from 20 medication-free rheumatoid arthritis patients were chemotactically hyporesponsive to 2 x 10(-8) M formyl-methionyl-leucyl-phenylalanine (f-MLP) as compared to 20 normal controls. They were relatively high producers of 5-hydroxyeicosatetraenoic acid (5-HETE) and low producers of leukotriene C4 (LTC4). Neutrophils from 10 patients treated with pirazolac (4-(4-chlorophenyl)-1-(4-fluorophenyl)-5-pyrazole acetic acid) showed increased chemotactic responsiveness concomitantly with normalization of 5-HETE and LTC4 production and a decrease in the clinical parameters of disease activity. Clinically attainable (30-60 micrograms/ml) in-vitro doses of pirazolac further depressed the chemotactic responsiveness of normal neutrophils treated with 10(-5)M f-MLP. Effects on endothelial gating of migrating neutrophil populations may explain this apparent contradiction between in-vivo and in-vitro actions of pirazolac on neutrophil chemotaxis.