The Mode of Action of Anti-inflammatory Steroids

  • Massimo Di Rosa
  • Luca Parente


Corticosteroids are widely used drugs, even though “with the exception of substitution therapy in deficient states, the use of corticosteroids and their congeners in disease is empirical.”1 These drugs are powerful anti-inflammatory agents, but their mode of action in inflammation is still controversial. Several hypotheses have been suggested, and it is likely that corticoids can interfere with several components of the inflammatory process.2 In the last decade increasing evidence has supported the role of arachidonic acid metabolites in inflammation.3 In this article we review the effects of corticosteroids on arachidonic acid metabolism.


Arachidonic Acid Arachidonic Acid Release Prostaglandin Biosynthesis Hydroxyeicosatetraenoic Acid Peritoneal Leukocyte 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Haynes RC, Murad F: Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of adrenocortical steroid biosynthesis, in Goodman Gilman A, Goodman L, Gilman A (eds): The Pharmacological Basis of Therapeutics, ed 6. New York, MacMillan, 1980, p 1466.Google Scholar
  2. 2.
    Dannenberg AM: The antiinflammatory effects of glucocorticosteroids. A brief review of the literature. Inflammation 3:329–343, 1979.Google Scholar
  3. 3.
    Vane JR: The mode of action of aspirin and similar compounds. J Allergy Clin Immunl 58: 691–712, 1976.CrossRefGoogle Scholar
  4. 4.
    Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature London New Biol 231:232–235, 1971.Google Scholar
  5. 5.
    Smith JB Willis AL: Aspirin selectively inhibits prostaglandin production in human platelets. Nature London New Biol 231:235–237, 1971Google Scholar
  6. 6.
    Ferreira SH, Moncada S, Vane JR: Indomethacin and aspirin abolish prostaglandin release from the spleen. Nature London New Biol 231: 237–239, 1971.CrossRefGoogle Scholar
  7. 7.
    Flower RJ: Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev 26: 33–67, 1974.PubMedGoogle Scholar
  8. 8.
    Flower RI, Gryglewski RJ, Herbaczynska-Cedro K, et al: Effects of anti-inflammatory drugs on prostaglandin biosynthesis. Nature London New Biol 238:104–106, 1972.Google Scholar
  9. 9.
    Herbaczynska-Cedro K, Staszewska-Barczak J: Adrenocortical hormones and the release of prostaglandin-like substances (PLS), in Abstracts of II Congress of Hungarian Pharmacological Society, Budapest, 1974, p 19.Google Scholar
  10. 10.
    Lewis GP, Piper PJ: Inhibition of release of prostaglandins as an explanation of some of the actions of anti-inflammatory corticosteroids. Nature 254: 308–311, 1975.PubMedCrossRefGoogle Scholar
  11. 11.
    Gryglewski Ri, Panczenko B, Korbut R, et al: Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins 10: 343–355, 1975.Google Scholar
  12. 12.
    Lewis GP, Piper PJ: Interactions of anti-inflammatory steroids with PG system in adipose tissue. Biochem Pharmacol 27: 1409–1412, 1978.PubMedCrossRefGoogle Scholar
  13. 13.
    Gryglewski RJ: Steroid hormones, anti-inflammatory steroids and prostaglandins. Pharmacol Res Commun 8: 337–348, 1976.PubMedCrossRefGoogle Scholar
  14. 14.
    Flower RJ, Blackwell GJ: The importance of phospholipase A2 in prostaglandin biosynthesis. Biochem Pharmacol 25:285–291, 1976.Google Scholar
  15. 15.
    Kantrowitz F, Robinson DR, McGuire MB, et al: Corticosteroids inhibit PG production by rheumatoid synovia. Nature 258: 737–739, 1975.PubMedCrossRefGoogle Scholar
  16. 16.
    Tashjian AH, Voelkel EF, McDonough J, et al: Hydrocortisone inhibits PG production by mouse fibrosarcoma cells. Nature 258: 739–741, 1975.PubMedCrossRefGoogle Scholar
  17. 17.
    Hong SL, Levine L: Inhibition of arachidonic acid from cells as the biochemical action of anti-inflammatory corticosteroids. Proc Nat Acad Sci USA 73: 1730–1734, 1976.PubMedCrossRefGoogle Scholar
  18. 18.
    Floman Y, Zor U: Mechanism of steroid action in inflammation: Inhibition of prostaglandin synthesis and release. Prostaglandins 12: 403–413, 1976.PubMedCrossRefGoogle Scholar
  19. 19.
    Piper PJ, Vane JR: Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs. Nature 223: 29–35, 1969.PubMedCrossRefGoogle Scholar
  20. 20.
    Svensson J, Hamberg M, Samuelsson B: Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets. Acta Physiol Scand 94: 222–228, 1975.PubMedCrossRefGoogle Scholar
  21. 21.
    Nijkamp FP, Flower RJ, Moncada S, et al: Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids. Nature 263: 479–482, 1976.PubMedCrossRefGoogle Scholar
  22. 22.
    Tam S, Hong SL, Levine L: Relationships, among the steroids, of anti-inflammatory properties and inhibition of prostaglandin production and arachidonic acid release by transformed mouse fibroblasts. J Pharmacol Exp Ther 203: 162–168, 1977.PubMedGoogle Scholar
  23. 23.
    Parente L, Ammendola G, Persico P, et al: Glucocorticosteroids, prostaglandins and the inflammatory process. Pol J Pharmacol Pharm 30:141–155, 1978.Google Scholar
  24. 24.
    Blackwell GJ, Flower RJ, Nijkamp FP, et al: Phospholipase A2 activity of guinea-pig isolated perfused lungs: Stimulation and inhibition by anti-inflammatory steroids. Br J Pharmacol 62: 79–89, 1978.PubMedGoogle Scholar
  25. 25.
    Weissmann G: Labilization and stabilization of lysosomes. Fed Proc 23:1038–1044, 1964.Google Scholar
  26. 26.
    Thompson EB, Lippman ME: Mechanism of action of glucocorticoids. Metabolism 23:159–202, 1974.Google Scholar
  27. 27.
    Jasani MK: Anti-inflammatory steroids: mode of action in rheumatoid arthritis and homograft reactions, in Vane JR, Ferreira SH (eds): Handbook of Experimental Pharmacology. New York, Springer-Verlag, 1979, vol 50/II, p 598.Google Scholar
  28. 28.
    Danon A, Assouline G: Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis. Nature 273: 552–554, 1978.PubMedCrossRefGoogle Scholar
  29. 29.
    Russo-Marie F, Paing M, Duval D: Involvement of glucocorticoid receptors in steroid-induced inhibition of prostaglandin secretion. J Biol Chem 254: 8498–8504, 1979.PubMedGoogle Scholar
  30. 30.
    Di Rosa M, Persico P: Mechanism of inhibition of prostaglandin biosynthesis by hydrocortisone in rat leucocytes. Br J Pharmacol 66: 161–163, 1979.PubMedGoogle Scholar
  31. 31.
    Flower RJ, Blackwell GJ: Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature 278: 456–459, 1979.PubMedCrossRefGoogle Scholar
  32. 32.
    Carnuccio R, Di Rosa M, Persico P: Hydrocortisone-induced inhibitor of prostaglandin biosynthesis in rat leucocytes. Br J Pharmacol 68: 14–16, 1980.PubMedGoogle Scholar
  33. 33.
    Blackwell GJ, Camuccio R, Di Rosa M, et al: Macrocortin: A polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature 287: 147–149, 1980.PubMedCrossRefGoogle Scholar
  34. 34.
    Hirata F, Schiffmann E, Venkatasubramanian K, et al: A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Nat Acad Sci USA 77: 2533–2536, 1980.PubMedCrossRefGoogle Scholar
  35. 35.
    Tsurufuji S: Gene expression as a molecular mechanism in the anti-inflammatory action of glucocorticoids. J Pharmacol Soc Korea 21: 115–117, 1977.Google Scholar
  36. 36.
    Tsurufuji S, Sugio K, Takemasa F: The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone. Nature 280: 408–410, 1979.PubMedCrossRefGoogle Scholar
  37. 37.
    Tsurufuji S, Kazuo S, Takemasa F, et al: Blockade by antiglucocorticoids, actinomycin D and cycloheximide of anti-inflammatory action of dexamethasone against bradykinin. J Pharmacol Exp Ther 212: 225–231, 1980.PubMedGoogle Scholar
  38. 38.
    Mentz P, Giessler CH, Forster W: Evidence for a direct inhibitory effect of glucocorticoids on the activity of phospholipase A2 as a further possible mechanism of some actions of steroidal anti-inflammatory drugs. Pharmacol Res Commun 12: 817–827, 1980.PubMedCrossRefGoogle Scholar
  39. 39.
    Moore PK, Hoult JRS: Anti-inflammatory steroids reduce tissue PG synthetase activity and enhance PG breakdown. Nature 288: 269–270, 1980.PubMedCrossRefGoogle Scholar
  40. 40.
    Chandrabose KA, Lapetina EG, Schmitges CJ, et al: Action of corticosteroids in regulation of prostaglandin biosynthesis in cultured fibroblasts. Proc Nat Acad Sci USA, 75: 214–217, 1978.PubMedCrossRefGoogle Scholar
  41. 41.
    Russo-Marie F, Seillan C, Duval D: Effect of dexamethasone on cyclooxygenase activity in renomedullary cells in culture. Agents Actions 10: 516–519, 1980.PubMedCrossRefGoogle Scholar
  42. 42.
    Samuelsson B: The leukotrienes: A new group of biologically active compounds including SRS-A. TIPS 1: 227–230, 1980.Google Scholar
  43. 43.
    Ford-Hutchinson AW, Bray MA, Doig MV, et al: Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286: 264–265, 1980.PubMedCrossRefGoogle Scholar
  44. 44.
    Palmer RMJ, Stepney RJ, Higgs GA, et al: Chemokinetic activity of arachidonic acid lipoxygenase products on leukocytes of different species. Prostaglandins 20: 411–418, 1980.PubMedCrossRefGoogle Scholar
  45. 45.
    Bray MA, Cunningham FM, Ford-Hutchinson AW, et al: Leukotriene B4 A mediator of vascular permeability. Br J Pharmacol 72: 483–486, 1981.PubMedGoogle Scholar
  46. 46.
    Wedmore CV, Williams TJ: Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature 289: 646–650, 1981.PubMedCrossRefGoogle Scholar
  47. 47.
    Dahlen SE, Hedquist P, Hammarstrom S, et al: Leukotrienes are potent constrictors of human bronchi. Nature 288: 484–486, 1980.PubMedCrossRefGoogle Scholar
  48. 48.
    Higgs GA, Flower RJ, Vane JR: A new approach to anti-inflammatory drugs. Biochem Pharmacol 28: 1959–1961, 1979.PubMedCrossRefGoogle Scholar
  49. 49.
    Hirata F, Del Carmine R, Nelson CA, et al: Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases. Proc Nat Acad Sci USA 78: 3190–3194, 1981.PubMedCrossRefGoogle Scholar
  50. 50.
    Korbut R, Ocetkiewicz A, Gryglewski RJ: The influence of hydrocortisone and indomethacin on the release of prostaglandin-like substances during circulatory shock in cats, which was induced by an intravenous administration of rabbit blood. Pharmacol Res Commun 10: 371–385, 1978.PubMedCrossRefGoogle Scholar
  51. 51.
    Hammarstrom S, Hamberg M, Duell EA, et al: Glucocorticoid in inflammatory proliferative skin disease reduces arachidonic and hydroxyeicosatetraenoic acids. Science 197: 994–996, 1977.PubMedCrossRefGoogle Scholar
  52. 52.
    Bombardieri S, Cattani P, Ciabattoni G, et al: The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs. Br J Pharmacol 73: 883–901, 1981.Google Scholar

Copyright information

© Plenum Publishing Corporation 1983

Authors and Affiliations

  • Massimo Di Rosa
    • 1
  • Luca Parente
    • 1
  1. 1.Institute of Experimental Pharmacology, Faculty of PharmacyUniversity of NaplesNaplesItaly

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