title: Abrogation of glucocorticoid-mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6, and IFN-gamma.
abstract: Glucocorticoids (GCS) inhibit the transcription of multiple activation-associated cytokine genes. By Northern blot analysis now we demonstrate that antiproliferative concentrations of dexamethasone and 6 alpha-methylprednisolone block mitogen-induced IL-2 gene expression in human peripheral blood mononuclear leukocytes in a concentration-dependent fashion. In addition, using a mitogen-induced proliferation assay of human peripheral blood mononuclear leukocytes, we show that GCS-mediated anti-proliferative effects are not blocked by rIL-1, rIL-2, rIL-3, rIL-4, rIL-5, rIL-6, rTNF-alpha, rTNF-beta, and rIFN-gamma, individually at 1 to 1000 U/ml, but are totally abrogated, in a concentration-dependent fashion, by the combination of rIL-1, rIL-6, and rIFN-gamma (25 to 50 U/ml for each cytokine). Thus, blockade of cytokine expression is the primary mechanism by which GCS inhibit mitogen-driven and alloantigen-induced T cell proliferation. The immunosuppressive effects of GCS are almost certainly exacted at the level of cytokine gene transcription.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: W Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: M L
authors.initials: ML
authors.lastname: Lipman
authors.forename: A C
authors.initials: AC
authors.lastname: Stevens
authors.forename: B
authors.initials: B
authors.lastname: Zanker
authors.forename: E T
authors.initials: ET
authors.lastname: Hadro
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
mesh_terms: D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D003907:Dexamethasone; D007371:Interferon-gamma