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 mug 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. BWA4C 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. (C) 2004 Elsevier B.V. All rights reserved.