Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells

作者: Tom L. Rowland , Simon M. McHugh , John Deighton , Rebecca J. Dearman , Pamela W. Ewan

DOI: 10.1016/S0162-3109(98)00010-1

关键词: Interleukin 10InterleukinDexamethasoneEndocrinologyInterleukin 4ThalidomideInterleukin 2Internal medicineInterleukin 6CytokineBiology

摘要: Immunosuppressive drugs are used routinely to reduce the inappropriate production of cytokines in an immune response. Recent attention has focused on that selectively inhibit specific cytokines. Both thalidomide and dexamethasone have been reported exhibit immunomodulatory effects vitro. We wished examine by peripheral blood mononuclear cells (PBMC), following mitogenic stimulation, at level both secreted product mRNA production. PBMC from healthy human volunteers were stimulated optimally with phytohaemagglutinin (PHA) presence varying concentrations using dimethyl sulphoxide (DMSO) as solvent. Analysis supernatants enzyme-linked immunosorbent assay (ELISA) showed caused a dose-dependent inhibition pro-inflammatory interleukin 6 (IL-6) tumour necrosis factor alpha (TNF-alpha), maximally reducing 20 (P < 0.05) 30% 0.01), respectively, compared controls. However, did not affect either proliferation or 2 (IL-2), 4 (IL-4) 10 (IL-10). A slight bell shaped interferon gamma (IFN-gamma) was seen which statistically significant 0.05). In contrast, inhibited markedly expression all tested (IL-2, IL-4, IL-6, IL-10, IFN-gamma TNF-alpha) fashion, levels near background. Reverse transcription-polymerase chain reaction (RT-PCR) analyses TNF-alpha IL-6 mRNA, whereas examined. The data indicate is broad range immunosuppressant inhibiting manner mRNA. Conversely, inhibits TNF-alpha. Due their different cytokine production, fact act transcription, we believe they influence separate pathways involved gene regulation.

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