TY - JOUR
T1 - Morphine directs T cells toward TH2 differentiation
AU - Roy, Sabita
AU - Balasubramanian, Sudha
AU - Sumandeep, S.
AU - Charboneau, Richard
AU - Wang, Jinghua
AU - Melnyk, Dean
AU - Beilman, Greg J.
AU - Vatassery, Rajan
AU - Barke, Roderick A.
N1 - Funding Information:
Supported by Grants from the Department of Defense/Veterans Affairs, the National Institutes of Health (Grant No. P50-DA 11806-01 and RO1 DA 12104), and the North Memorial Trauma Institute.
PY - 2001
Y1 - 2001
N2 - Background. 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 TH2 differentiation. We tested the hypothesis that morphine treatment after injury promotes TH2 differentiation of precursor T cells through the μ-opioid receptor. Methods. Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or μ-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 TH1 (interleukin-2 [IL-2], interferon γ [IFNγ]) and TH2 (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. Results. Morphine treatment of PBMCs decreases IL-2 and IFNγ and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFNγ and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in μ-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. Conclusions. We conclude that morphine treatment promotes TH2 differentiation through a μ-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism.
AB - Background. 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 TH2 differentiation. We tested the hypothesis that morphine treatment after injury promotes TH2 differentiation of precursor T cells through the μ-opioid receptor. Methods. Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or μ-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 TH1 (interleukin-2 [IL-2], interferon γ [IFNγ]) and TH2 (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. Results. Morphine treatment of PBMCs decreases IL-2 and IFNγ and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFNγ and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in μ-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. Conclusions. We conclude that morphine treatment promotes TH2 differentiation through a μ-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism.
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U2 - 10.1067/msy.2001.116033
DO - 10.1067/msy.2001.116033
M3 - Article
C2 - 11490364
AN - SCOPUS:0034905665
SN - 0039-6060
VL - 130
SP - 304
EP - 309
JO - Surgery
JF - Surgery
IS - 2
ER -