Blockade of leukotriene B4 prevents articular incapacitation in rat zymosan-induced arthritis.

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(4)C (N-(3-phenoxycinnamyl)-acetohydroxamic acid--2 h after the zymosan; 10 microg 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(4)C 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.