Effect of a leukotriene B4 receptor antagonist on leukotriene B4-induced neutrophil chemotaxis in cavine dermis.

Leukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated as a mediator in a number of inflammatory diseases. When injected intradermally into the cavine. LTB4 elicits a dose-dependent immigration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4-dihydro-8-p ropyl-2H- 1-benzopyran-2-carboxylic acid), a potent LTB4 receptor antagonist inhibited the chemotactic actions of LTB4 when coadministered into the dermal site and when given intravenously or orally with ED50 values of 200 ng, 0.5 mg/kg, and 0.6 mg/kg respectively. This compound may well have application in disease states, such as inflammatory bowel disease and psoriasis, where LTB4 is implicated as a proinflammatory mediator.