A lethal role of platelet activating factor in anaphylactic shock in mice

Abstract

The lethal role of platelet activating factor (PAF) in anaphylactic shock was examined in mice, using the specific PAF antagonist, CV-3988. CV-3988 (0.3-3 mg/kg i.v.), given 5 min before PAF, protected mice from death (ED50, 0.9 mg/kg). CV-3988 (3 mg/kg i.v.), given 1 min after PAF was injected, was also effective, but no so effective when given 5 min later. Dexamethasone (2 mg/kg i.v. 3 hr before the PAF-injection), naloxone (1 and 10 mg/kg i.v. 5 min before), FPL-55712 (10 mg/kg i.v. 5 min before) and BW-755c (300 mg/kg p.o. 1 hr before) also improved the survival rate, but aspirin (100 mg/kg p.o. 1 hr before) did not. In anaphylactic shock, CV-3988 (0.3-3 mg/kg i.v.), given 5 min before and 5 min after rechallenge with antigen protected the sensitized mice from death (ED50, 1.2 and 0.48 mg/kg, respectively). Dexamethasone and naloxone protected mice from anaphylactic shock, but BW-755c and FPL-55712 had no protective effects. In contrast to CV-3988, dexamethasone and naloxone were ineffective when given 5 min after the rechallenge. Congestion of the lung, kidney and heart and infiltration of neutrophils in the lung were marked in mice with PAF-induced and anaphylactic shock. The related histology showed an improvement with CV-3988. These results strongly suggest that PAF may play a lethal role in anaphylactic shock and that CV-3988 may be an effective preventing agent.