Is platelet activating factor (PAF) a mediator of endotoxin shock?

To determine whether endogenous PAF contributes to the pathogenesis of endotoxin shock, CV-3988, a specific PAF antagonist, was injected i.v. to rats before, simultaneously with or after endotoxin. CV-3988 (5 mg/kg i.v.) injected 5 min before the endotoxin completely inhibited endotoxin (15 mg/kg i.v.)-induced hypotension, and CV-3988 (0.05-1 mg/kg i.v.) injected 7-10 min after the endotoxin rapidly reversed endotoxin-induced hypotension. A combination of CV-3988 (10 mg/kg) with endotoxin (5 mg/kg) administered i.v. improved the survival rate for 20 h or more. CV-3988 (0.05-1 mg/kg i.v.) rapidly reversed the PAF (1 microgram/kg i.v.)-induced hypotension. These findings strongly suggest that endogenous PAF may play a pivotal role in the pathogenesis of endotoxin shock.