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. 1988 Apr;85(7):2315–2319. doi: 10.1073/pnas.85.7.2315

Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release.

J Raud 1, S E Dahlén 1, A Sydbom 1, L Lindbom 1, P Hedqvist 1
PMCID: PMC279982  PMID: 2451246

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aspinall R. L., Cammarata P. S. Effect of prostaglandin E2 on adjuvant arthritis. Nature. 1969 Dec 27;224(5226):1320–1321. doi: 10.1038/2241320a0. [DOI] [PubMed] [Google Scholar]
  2. Bray M. A., Cunningham F. M., Ford-Hutchinson A. W., Smith M. J. Leukotriene B4: a mediator of vascular permeability. Br J Pharmacol. 1981 Mar;72(3):483–486. doi: 10.1111/j.1476-5381.1981.tb11000.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burka J. F., Eyre P. Modulation of the formation and release of bovine SRS-A in vitro by several anti-anaphylactic drugs. Int Arch Allergy Appl Immunol. 1975;49(6):774–781. doi: 10.1159/000231461. [DOI] [PubMed] [Google Scholar]
  4. Engineer D. M., Niederhauser U., Piper P. J., Sirois P. Release of mediators of anaphylaxis: inhibition of prostaglandin synthesis and the modification of release of slow reacting substance of anaphylaxis and histamine. Br J Pharmacol. 1978 Jan;62(1):61–66. doi: 10.1111/j.1476-5381.1978.tb07006.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fantone J. C., Kunkel S. L., Ward P. A., Zurier R. B. Suppression by prostaglandin E1 of vascular permeability induced by vasoactive inflammatory mediators. J Immunol. 1980 Dec;125(6):2591–2596. [PubMed] [Google Scholar]
  6. Ham E. A., Soderman D. D., Zanetti M. E., Dougherty H. W., McCauley E., Kuehl F. A., Jr Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4349–4353. doi: 10.1073/pnas.80.14.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Higgs G. A., Eakins K. E., Mugridge K. G., Moncada S., Vane J. R. The effects of non-steroid anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation. Eur J Pharmacol. 1980 Aug 22;66(1):81–86. doi: 10.1016/0014-2999(80)90297-6. [DOI] [PubMed] [Google Scholar]
  8. Hitchcock M. Effect of inhibitors of prostaglandin synthesis and prostaglandins E2 and F2alpha on the immunologic release of mediators of inflammation from actively sensitized guinea-pig lung. J Pharmacol Exp Ther. 1978 Nov;207(2):630–640. [PubMed] [Google Scholar]
  9. Kaliner M., Austen K. F. Cyclic AMP, ATP, and reversed anaphylactic histamine release from rat mast cells. J Immunol. 1974 Feb;112(2):664–674. [PubMed] [Google Scholar]
  10. Koopman W. J., Orange R. P., Austen K. F. Prostaglandin inhibition of the immunologic release of slow reacting substance of anaphylaxis in the rat. Proc Soc Exp Biol Med. 1971 May;137(1):64–67. doi: 10.3181/00379727-137-35512. [DOI] [PubMed] [Google Scholar]
  11. Lee T. H., Israel E., Drazen J. M., Leitch A. G., Ravalese J., 3rd, Corey E. J., Robinson D. R., Lewis R. A., Austen K. F. Enhancement of plasma levels of biologically active leukotriene B compounds during anaphylaxis in guinea pigs pretreated by indomethacin or by a fish oil-enriched diet. J Immunol. 1986 Apr 1;136(7):2575–2582. [PubMed] [Google Scholar]
  12. Okazaki T., Ilea V. S., Rosario N. A., Reisman R. E., Arbesman C. E., Lee J. B., Middleton E., Jr Regulatory role of prostaglandin E in allergic histamine release with observations on the responsiveness of basophil leukocytes and the effect of acetylsalicylic acid. J Allergy Clin Immunol. 1977 Dec;60(6):360–366. doi: 10.1016/0091-6749(77)90067-7. [DOI] [PubMed] [Google Scholar]
  13. Rampart M., Williams T. J. Polymorphonuclear leukocyte-dependent plasma leakage in the rabbit skin is enhanced or inhibited by prostacyclin, depending on the route of administration. Am J Pathol. 1986 Jul;124(1):66–73. [PMC free article] [PubMed] [Google Scholar]
  14. SHORE P. A., BURKHALTER A., COHN V. H., Jr A method for the fluorometric assay of histamine in tissues. J Pharmacol Exp Ther. 1959 Nov;127:182–186. [PubMed] [Google Scholar]
  15. Svensjö E., Arfors K. E., Arturson G., Rutili G. The hamster cheek pouch preparation as a model for studies of macromolecular permeability of the microvasculature. Ups J Med Sci. 1978;83(1):71–79. doi: 10.3109/03009737809179115. [DOI] [PubMed] [Google Scholar]
  16. Weissmann G., Smolen J. E., Korchak H. Prostaglandins and inflammation: receptor/cyclase coupling as an explanation of why PGEs and PGI2 inhibit functions of inflammatory cells. Adv Prostaglandin Thromboxane Res. 1980;8:1637–1653. [PubMed] [Google Scholar]
  17. Williams T. J., Peck M. J. Role of prostaglandin-mediated vasodilatation in inflammation. Nature. 1977 Dec 8;270(5637):530–532. doi: 10.1038/270530a0. [DOI] [PubMed] [Google Scholar]

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