Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms. NLM AIDSLINE Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

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Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms.

Am J Respir Cell Mol Biol. 1996 Apr;14(4):388-97. Unique Identifier : AIDSLINE MED/96186980
Krouwels FH; van der Heijden JF; Lutter R; van Neerven RJ; Jansen HM; Out TA; Department of Pulmonology, Clinical and Laboratory Immunology; Unit, Academic Medical Center, University of Amsterdam, The; Netherlands.

Abstract: Glucocorticosteroids (GCS) are beneficial in allergic asthma. GCS therapy results in reduced mRNA expression of interleukin-4 (IL-4) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. In vitro studies with blood-derived T cells, however, show inhibition of all three cytokines by GCS. We studied the effects of GCS on T cells from BAL in vitro, namely Th0-, Th1, and Th2-like clones; and we compared BAL- with blood-derived clones. Dexamethasone (DEX) inhibited the anti-CD3-induced production of IL-4, IL-5 and IFN-gamma in all 20 clones tested. IFN-gamma production was inhibited significantly less than IL-4 and IL-5. DEX enhanced the ratio IFN-gamma/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers DEX inhibited IL-2 production partially and enhanced IL-2R alpha expression and proliferation. Anti-IL-2 and anti-IL2R alpha blocked the DEX-induced increase in proliferation. High levels of added IL-2 induced the second type of response. In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by DEX than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. The differential effects of DEX on the proliferation of high and low IL-2 producers in vitro may implicate a selective outgrowth of Th1-like T cells in vivo in patients treated with steroids.
Keywords: Antibodies/PHARMACOLOGY Antigens, CD3/IMMUNOLOGY Bronchoalveolar Lavage Fluid/*CYTOLOGY Cells, Cultured Comparative Study Cytokines/*BIOSYNTHESIS Dexamethasone/*PHARMACOLOGY Glucocorticoids, Synthetic/*PHARMACOLOGY Human Interferon Type II/BIOSYNTHESIS Interleukin-2/BIOSYNTHESIS/METABOLISM Interleukin-4/BIOSYNTHESIS Interleukin-5/BIOSYNTHESIS Kinetics Receptors, Interleukin-2/PHYSIOLOGY Support, Non-U.S. Gov't T-Lymphocytes/*DRUG EFFECTS/PHYSIOLOGY Th1 Cells/*DRUG EFFECTS/PHYSIOLOGY JOURNAL ARTICLEKWDantibodies/pharmacologyantigens,cd3/immunologybronchoalveolarlavagefluid/KWDcytologycells,culturedcomparativestudycytokines/KWDbiosynthesisdexamethasone/KWDpharmacologyglucocorticoids,synthetic/KWDpharmacologyhumaninterferontypeii/biosynthesisinterleukin-2/biosynthesis/metabolisminterleukin-4/biosynthesisinterleukin-5/biosynthesiskineticsreceptors,interleukin-2/physiologysupport,non-uKWDsKWDgov'tt-lymphocytes/KWDdrugeffects/physiologyth1cells/KWDdrugeffects/physiologyjournalarticle
960730
M9670475

Copyright © 1996 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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