Effect of the PAF-antagonist WEB 2086 on anaphylactic lung reaction: comparison of inhalative and intravenous challenge.

The specific and potent antagonist of platelet activating factor (PAF), WEB 2086, has been used to investigate the putative role of PAF in anaphylaxis in the guinea-pig. Intravenous (i.v.) challenge with ovalbumin has been compared to inhalative provocation. When actively sensitized guinea-pigs were challenged by the i.v. route, in the presence of mepyramine (5 micrograms/kg i.v.), oral WEB 2086 (0.05-0.5 mg/kg) inhibited the anaphylactic bronchoconstriction but not the hypotension. In passively sensitized guinea-pigs, i.v. WEB 2086, in the presence of mepyramine, protected the animals from both anaphylactic bronchoconstriction and blood pressure changes. When the antigen was inhaled by actively sensitized guinea-pigs, WEB 2086 inhibited the anaphylactic reaction without the administration of any additional antihistamine. These results suggest that PAF plays an important role in anaphylaxis. PAF may be (a) more important in passive than in active anaphylaxis and (b) may be involved during inhalative challenge in active anaphylaxis.