Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release.
Intravital microscopy and determination of in vivo histamine release revealed that the cyclooxygenase inhibitor indomethacin reduced antigen-induced vasodilation while enhancing plasma extravasation, leukocyte accumulation, and histamine release in cheek pouches of immunized hamsters. Topical application of prostaglandin E2 (PGE2, 30 nM) totally reversed the indomethacin-induced potentiation of the inflammatory reaction to antigen challenge and suppressed both the histamine release and plasma leakage also in the absence of indomethacin. On the other hand, PGE2, which per se caused vasodilation, markedly potentiated the postcapillary leakage of plasma induced by histamine or leukotriene C4, as well as the leukocyte activation and subsequent plasma extravasation evoked by leukotriene B4. Taken together, the data indicate that PGE2 reduced the antigen response by suppression of mediator release from the numerous mast cells present in the cheek pouch. Moreover, the PGE2-sensitive potentiation by indomethacin of the antigen response suggests that endogenous vasodilating prostaglandins (possibly PGE2) predominantly were anti-inflammatory.
D000818:Animals; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006968:Hypersensitivity, Delayed / Q000473:pathology*; D007213:Indomethacin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced*; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D013189:SRS-A; D007975:Leukotriene B4; D006632:Histamine; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin