Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4

James Goodwin, D. Atluru, S. Sierakowski, E. A. Lianos

Research output: Contribution to journalArticle

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Abstract

The mechanism whereby glucocorticosteroids are immunosuppressive is unknown. One potential mechanism of action of these compounds is inhibition of arachidonic acid metabolism. We found that the inhibition of lymphocyte proliferation by hydrocortisone or dexamethasone was mimicked by nonspecific lipoxygenase inhibitors and also by a specific 5- lipoxygenase inhibitor, but not by a specific cyclooxygenase inhibitor. Mitogen-stimulated cultures of T cells produce ~ 5 x 10-9 M leukotriene B4 (LTB4) in 24 h. This production of LTB4 is completely inhibited by concentrations of hydrocortisone or lipoxygenase inhibitors that inhibit mitogen-induced [3H]thymidine incorporation. The inhibition of lymphocyte proliferation by either hydrocortisone or by the 5-lipoxygenase inhibitor was totally reversed by LTB4 but not by leukotriene C4 or leukotriene D4. LTB4 had no effect on the inhibition of lymphocyte proliferation by noncorticosteroids such as prostaglandin E2, histamine, or γ-interferon. The inhibition of interleukin 2 (IL-2) production by hydrocortisone or dexamethasone was also completely reversed by exogenous LTB4. LTB4 alone did not cause IL-2 production or cell proliferation when added to resting lymphocytes. Thus, endogenous LTB4 production appears to be necessary but not sufficient for phytohemagglutinin-induced IL-2 production and lymphocyte proliferation. Glucocorticosteroids inhibit IL-2 production and lymphocyte proliferation by inhibiting endogenous LTB4 production.

Original languageEnglish (US)
Pages (from-to)1244-1250
Number of pages7
JournalJournal of Clinical Investigation
Volume77
Issue number4
StatePublished - 1986
Externally publishedYes

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Leukotriene B4
Interleukin-2
Hydrocortisone
Cell Proliferation
T-Lymphocytes
Lipoxygenase Inhibitors
Lymphocytes
Mitogens
Dexamethasone
Leukotriene D4
Leukotriene C4
Cyclooxygenase Inhibitors
Phytohemagglutinins
Immunosuppressive Agents
Dinoprostone
Arachidonic Acid
Thymidine
Interferons
Histamine
Action Potentials

ASJC Scopus subject areas

  • Medicine(all)

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Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4 . / Goodwin, James; Atluru, D.; Sierakowski, S.; Lianos, E. A.

In: Journal of Clinical Investigation, Vol. 77, No. 4, 1986, p. 1244-1250.

Research output: Contribution to journalArticle

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