Document Detail


Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4.
MedLine Citation:
PMID:  3007577     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 approximately 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 gamma-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.
Authors:
J S Goodwin; D Atluru; S Sierakowski; E A Lianos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  77     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1986 Apr 
Date Detail:
Created Date:  1986-05-14     Completed Date:  1986-05-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1244-50     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Arachidonate Lipoxygenases
Arachidonic Acids / pharmacology
Cell Division / drug effects
Chromatography, High Pressure Liquid
Cyclooxygenase Inhibitors
Dexamethasone / pharmacology*
Dinoprostone
Histamine / pharmacology
Hydrocortisone / pharmacology*
Interferon-gamma / pharmacology
Interleukin-2 / biosynthesis*
Leukotriene B4 / pharmacology
Lipoxygenase Inhibitors
Phytohemagglutinins / pharmacology
Prostaglandins E / pharmacology
T-Lymphocytes / cytology*,  metabolism
Thymidine / metabolism
Grant Support
ID/Acronym/Agency:
AG01245-06/AG/NIA NIH HHS; AM34672-01/AM/NIADDK NIH HHS; AM34793-01/AM/NIADDK NIH HHS
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Cyclooxygenase Inhibitors; 0/Interleukin-2; 0/Lipoxygenase Inhibitors; 0/Phytohemagglutinins; 0/Prostaglandins E; 363-24-6/Dinoprostone; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; 50-89-5/Thymidine; 51-45-6/Histamine; 71160-24-2/Leukotriene B4; 82115-62-6/Interferon-gamma; EC 1.13.11.-/Arachidonate Lipoxygenases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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