Morphine directs T cells toward TH2 differentiation

Sabita Roy, Sudha Balasubramanian, S. Sumandeep, Richard Charboneau, Jinghua Wang, Dean Melnyk, Greg J. Beilman, Rajan Vatassery, Roderick A. Barke

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)304-309
Number of pages6
Issue number2
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Surgery


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