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• W2019960613 abstract "Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures and to be the result, in part, of a redirection of CD4(+) T cells toward T(H2) differentiation. We tested the hypothesis that morphine treatment after injury promotes T(H2) differentiation of precursor T cells through the mu-opioid receptor.Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or mu-opioid receptor knock-out mice were treated in vitro with either vehicle or morphine and then stimulated with anti-CD3/anti-CD28. The supernatant was assayed for T(H1) (interleukin-2 [IL-2], interferon gamma [IFN gamma]) and T(H2) (IL-4, IL-5) cytokines (enzyme-linked immunosorbent assay). Morphine regulation of IL-4 transcription was investigated in PBMCs (IL-4 messenger RNA, nuclear factor of activated T-cells) and Jurkat T cells transfected with a murine IL-4 promoter-luciferase construct. Morphine-induced nuclear factor of activated T-cell (NFAT) binding was assayed with the electromobility shift assay in Jurkat T cells.Morphine treatment of PBMCs decreases IL-2 and IFN gamma and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFN gamma and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in mu-opioid receptor knockout mice. Morphine treatment increases IL-4 messenger RNA accumulation in PBMCs and increases IL-4 promoter activity in Jurkat T cells. Morphine increases NFAT nuclear protein binding to an NFAT DNA response element.We conclude that morphine treatment promotes T(H2) differentiation through a mu-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism." @default.
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• W2019960613 date "2001-08-01" @default.
• W2019960613 modified "2023-10-14" @default.
• W2019960613 title "Morphine directs T cells toward Th2 differentiation" @default.
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• W2019960613 doi "https://doi.org/10.1067/msy.2001.116033" @default.
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