Abrogation of glucocorticoid-mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6, and IFN-gamma

• Published in: The Journal of immunology (1950) Vol. 146; no. 10; pp. 3523 - 3527
• Main Authors: Almawi, WY, Lipman, ML, Stevens, AC, Zanker, B, Hadro, ET, Strom, TB
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.1991
• Subjects: Cells, Cultured; Dexamethasone - pharmacology; Drug Synergism; Humans; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Interleukin-2 - genetics; Interleukin-6 - pharmacology; Lymphocyte Activation - drug effects; Recombinant Proteins - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Transcription, Genetic - drug effects
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.146.10.3523

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.