LEXIPAFANT (BB-882), A PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST, AMELIORATES MUCOSAL INFLAMMATION IN AN ANIMAL-MODEL OF COLITIS

Objective: To assess the anti-inflammatory action of lexipafant (BB-88 2), a platelet activating factor antagonist, in an animal model of acu te colitis. Design: An animal intervention study. Methods: Following t he rectal instillation of formalin 0.75% into male New Zealand White ( NZW) rabbits, 0.85 mi of aggregated immunoglobulin was administered i. v. Treatment groups (0.8 mg/kg, n=6; 2.4 mg/kg, n=13; 3.2 mg/kg, n=10) were given bolus doses of BB-882 two-hourly i.v. (control group, n=25 ). Rectal dialysis was performed before induction of colitis and sacri fice. Dialysate leukotriene B-4 (LTB(4)), prostaglandin E(2) (PGE(2)) and thromboxane B-2 (TXB(2)) levels were determined. Tissue was saved for histology and measurement of myeloperoxidase content. Results: The re was a dose-dependent improvement in macroscopic scores (2.4 and 3.2 mg/kg: P<0.02, P<0.001) and myeloperoxidase levels (3.2 mg/kg: P<0.04 ). Dialysate LTB(4) levels fell (2.4 and 3.2 mg/kg: P<0.03, P<0.02) as did PGE(2) levels. TXB(2) concentrations remained unaffected. Conclus ion: The PAF receptor antagonist BB-882 shows efficacy in treating inf lammation in an animal model of acute colitis as evidenced by a dose-d ependent fall in macroscopic mucosal damage, neutrophil infiltration a nd reduced generation of inflammatory mediators.