Effect of immunization with prostaglandin metabolites on gastrointestinal ulceration

Active immunization of rabbits with a 6-ketoprostaglandin F1 alpha-thyroglobulin conjugate induced gastrointestinal ulceration, whereas active immunization of rabbits with 13,14-dihydro-15-keto prostaglandin E2-thyroglobulin conjugate or with thyroglobulin alone did not result in ulceration. Passive immunization of a separate group of rabbits with 6-ketoprostaglandin F1 alpha-hyperimmune plasma, obtained from actively 6-ketoprostaglandin F1 alpha-immunized donor rabbits that had ulcers, induced gastric ulceration within 9 days, whereas passive immunization of rabbits with control plasma, obtained from donor rabbits actively immunized with thyroglobulin alone, did not induce ulceration. Ulcerogenic donor plasma containing antibody to 6-ketoprostaglandin F1 alpha neutralized the inhibitory actions of prostacyclin on adenosine diphosphate-induced platelet aggregation, indicating that this antibody cross-reacted with prostacyclin. In contrast, plasma containing antibodies to 13,14-dihydro-15-ketoprostaglandin E2 cross-reacted only slightly with prostaglandin E2. Thus antibodies to inactive metabolites of prostaglandins induce ulceration only if these antibodies cross-react with an endogenous, "cytoprotective" prostaglandin.