Glucocorticoid protection against PAF-acether toxicity in mice

Intravenous platelet activating factor (PAF-acether, 10 to 25 micrograms/kg body weight) produced dose-dependent mortality in both male and female mice. Pretreatment with indomethacin (50 mg/kg), verapamil (40 mg/kg) or nifedipine (4 mg/kg) failed to inhibit the lethal effect of 20 micrograms/kg PAF-acether. This suggests that neither arachidonate cyclo-oxygenase products nor availability of extracellular Ca2+ mediate the toxic action. In contrast, pretreatment with 100 mg/kg cortisone acetate (s.c.) daily for four days exerted a highly protective effect, i.e. 100% and 93% survival in males and females, compared to 13% and 7% respectively, in untreated animals. PAF-acether-induced death may be a useful model for the in vivo evaluation of pharmacological agents in anaphylactic shock.