INVOLVEMENT OF LEUKOTRIENE B-4 IN MURINE DERMATITIS MODELS

Leukotriene B-4 (LTB4) is a product of the 5-lipoxygenase pathway of a rachidonic acid (AA) metabolism. LTB4 is a potent chemotactic factor f or neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis, pso riasis, and inflammatory bowel disease. To investigate the role of LTB 4 in dermatitis, we used S-(4-dimethylaminobenzyl)-N-[(2S) -mercapto-2 -methylpropionyl]-L-cysteine (SA6541), a potent leukotriene A(4) (LTA( 4)) hydrolase inhibitor. SA6541 inhibited LTB4 production with an IC50 value of 270 nM in vitro. 5-Hydroperoxyeicosatetraenoic acid (5-HPETE ) or AA injection induced LTB4 production and neutrophil influx in mou se ear. SA6541 inhibited 5-HPETE- and AA-induced LTB4 production and n eutrophil influx in mouse ear when administered orally at a dose of 50 mg/kg. SA6541 also inhibited 5-HPETE induced prostaglandin E-2 (PGE(2 )) production, probably by an indirect effect through the inhibition o f LTB4 production. These results suggest that LTB4 map be important in the pathogenesis of dermatitides such as psoriasis. (C) 1998 Elsevier Science Inc.