INVIVO ALLERGEN TACHYPHYLAXIS IN GUINEA-PIG LUNG IS MEDIATED BY ENDOGENOUS PROSTAGLANDIN-E BIOSYNTHESIS

The term allergen tachyphylaxis (AT) describes a progressively decreased bronchial reactivity to allergen exposition after repeated allergen challenge [in this test system measured by sequential inhalative antigen challenge of sensitized guinea pigs (GP)]. The hypothesis that AT is mediated by endogenous prostaglandin E (PGE) biosynthesis was tested in vivo on GP sensitized to ovalbumin (OA). Different groups of animals were challenged with simultaneous inhalation of OA (repeatedly at time 0, 10, 20, 60 and 70 min) together with inhibitors of PGE-biosynthesis (p-chloromercurobenzoic acid = PCMB, copper sulfate = Cu, copper dithiotreitol complex = CuDTT, dithiotreitol = DTT and dimercaptopropanol = DMP) or agents increasing PGE production (aurothioglucose = Au, zinc dithiotreitol compex = ZnDTT and reduced glutathion = GSH). Bronchial obstruction was measued by whole body plethysmography. PCMB, Cu, CuDTT, DTT and DMP inhibited AT; Au and ZnDTT enhanced AT. Acetylsalicylic acid (ASA) treatment prevented AT. Aerosols of PGE2 but not of prostacyclin or prostaglandin D2 restored AT in ASA treated animals. In addition to these in vivo experiments in vitro investigations showed that PCMB, Cu and DTT decreased while ZnDTT increased PGE biosynthesis of allergen challenged GP lungs. Thus AT, an important self-protecting mechanism of GP bronchial asthma, is mediated at least in part via endogenous PGE.