Effects of beta2 adrenoceptor agonists on T-cell subpopulations.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Effects of beta2 adrenoceptor agonists on T-cell subpopulations.

APMIS. 1998 Sep;106(9):849-57. Unique Identifier : AIDSLINE MED/99023597
Holen E; Elsayed S; Allergy Research Group, Department of Clinical Biochemistry,; University Hospital, Bergen, Norway.

Abstract: The aim of the present communication is to determine the effects of beta2 adrenoceptor agonists on growth and cytokine secretion using allergen-specific T cells. Four beta2 adrenoceptor agonists were administered at therapeutically relevant doses (salbutamol 1-2 microM; salmeterol 0.03-0.06 microM; terbutaline 0.56-1.12 microM, and fenoterol 0.7-1.4 microM to: a) Cultures of human peripheral mononuclear cells (PBMC) b) Positively selected CD4+ and CD8+ subsets, c) Allergen-specific T-cell lines (TCL). Drug effects on growth kinetics and the secretion of IL-4, IL-5, INF-gamma and IgE following T-cell stimulation were investigated. Comparing the growth inhibitory effect of the 4 beta2 agonists at 2 different concentrations, using 12 PBMC, 10 CD4+ and CD8+ and 10 TCL cultures, the following patterns were observed: PBMC-, CD4+- and CD8+-cultures: salmeterol, followed by salbutamol and fenoterol, was a more potent inhibitor than terbutaline. In long-term TCL-cultures, salmeterol was the most potent drug, followed by fenoterol. No significant differences were observed between salbutamol and terbutaline. TCL secretion of IL-4 and IL-5 (TH2 cytokines) was also significantly inhibited. In one patient, INF-gamma secretion (TH1/THO cytokine) could be enhanced by drug administration. High IgE secretion, from 1% remaining B cells in one of the patients, following PHA+IL-2 stimulation, could be reduced by the drugs. The results showed that the beta2 agonists could influence T-cell growth and function. The changes regarding cell function were individual and related to T-cell phenotypes secreting TH1/THO or TH2 cytokines. These results suggest that administration of beta2 adrenoceptor agonists could be beneficial, not only for bronchodilation, but also for suppressing the underlying inflammatory process dominated by TH2-like cytokine secretion.

Keywords: JOURNAL ARTICLE Adrenergic beta-Agonists/*PHARMACOLOGY Albuterol/ANALOGS & DERIVATIVES/PHARMACOLOGY Allergens/*IMMUNOLOGY Cell Line Cells, Cultured Cytokines/ANALYSIS CD4-Positive T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY CD8-Positive T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY Fenoterol/PHARMACOLOGY Human IgE/ANALYSIS Interleukin-2/PHARMACOLOGY Leukocytes, Mononuclear/*DRUG EFFECTS/IMMUNOLOGY Lymphocyte Transformation/DRUG EFFECTS Phytohemagglutinins/PHARMACOLOGY Receptors, Adrenergic, beta-2/*AGONISTS Terbutaline/PHARMACOLOGY
990130
A9911013

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