Blockade of leukotriene B 4 prevents articular incapacitation in rat zymosan-induced arthritis

Abstract

We investigated whether leukotrienes mediate cell influx and articular incapacitation in zymosan-induced arthritis. Rats received 1 mg zymosan intra-articularly (i.a.). The hyperalgesia was measured using the rat articular incapacitation test. Cell influx, leukotriene B 4 and prostaglandin E 2 levels were assessed in the joint exudate, at 6 h. Groups received either the leukotriene B 4 synthesis inhibitor MK 886 (3-[1-(4-chlorobenzyl)-3- t-butyl-thio-5-isopropylindol-2-yl)]-2,2-dimethylpropanoic acid 30 min before or 2 h after the zymosan; 0.3–3 mg kg −1 i.p.), the leukotrienes synthesis inhibitor BWA 4C ( N-(3-phenoxycinnamyl)-acetohydroxamic acid—2 h after the zymosan; 10 μg i.a.) or the peptido-leukotrienes antagonist sodium montelukast (30 min before and 2 h after the zymosan; 10 mg kg −1 per os). MK 886 inhibited the articular incapacitation and cell influx, while reducing leukotriene B 4, but not prostaglandin E 2 levels. BWA 4C inhibited the articular incapacitation. Sodium montelukast did not affect either of the parameters. The data suggest that leukotriene B 4 is involved in cell influx and articular incapacitation in zymosan arthritis.