Effect of different concentrations of morphine and tramadol on the differentiation of human helper T cells in vitro

Abstract

Editor—We investigated the effect of different concentrations of morphine and tramadol on the differentiation of human adult helper T cells in vitro. Twenty outpatients without any immune diseases were selected and their peripheral blood was collected. Whole blood or peripheral blood mononuclear cells (PBMCs) were pretreated with different concentrations of morphine or tramadol for 48 h, while the control group received neither. The ratio of CD4+IFN-γ+IL-2+/CD4+IL-4+IL-10+ was analysed by three-color flow cytometry.1Carrock SWA North ME Webser DB et al.Determination of intracellular cytokines by flow-cytometry following whole-blood culture.J Immunol Methods. 1997; 209: 67-72Crossref PubMed Scopus (60) Google Scholar The intracellular cytokines, after stimulation with PMA and Ionomycin (Ion), were detected by trace whole blood technology. The CD4+CCR5+ and CD4+ CCR3+ cells in PBMCs were counted in order to observe the imbalance of Th1/Th2. After treatment with morphine or tramadol, the number of Th2 increased significantly and the ratio of Th1/Th2 decreased dramatically in both groups. At the same time the number of CD4+IFN-γ+ IL-2+ cells decreased and CD4+IL-4+IL-10+ cells increased sharply as compared with the control group. Both morphine and tramadol can direct Th0 cells toward Th2, especially morphine. The Th2 redirection, as well as the changes in cytokines, showed a dose dependent fashion in both drugs. Although tissue wound or seriously surgical stress is thought to be one of the most important reasons for immune suppression, anaesthetic agents used in these patients also play a part in the modulation of immune response.2Roy S Balasubramanian S Linda F et al.Morphine direct T cells toward Th2 differentiation.Surgery. 2002; 130: 304-309Abstract Full Text Full Text PDF Scopus (88) Google Scholar There is reasonable evidence that analgesic agents can inhibit immune function, especially opioids.3Pang WW Mok MS Lin CH et al.Comparison of patient controlled analgesia (PCA) with tramadol or morphine.Can J Anaesth. 1999; 46: 1030-1035Crossref PubMed Scopus (72) Google Scholar4Eisenstein TK Hilburger ME Opioid modulation of immune responses: effect on phagocyte and lymphoid cell populations.J Neuroimmunol. 1998; 83: 36-44Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar Our study demonstrated a remarkable Th2 differentiation after pretreatment with morphine or tramadol. IL-4 and IL-10 elevated significantly while IL-2 and IFN-γ decreased significantly compared with control groups. We also found that the suppression of cell-mediated immunity was dose dependent. It indicates that excessively high concentration of these drugs should be avoided in clinical applications in order to maintain a healthy Th1/Th2 balance. Nair and colleagues5Nair MP Schwartz SA Mackay CR et al.Immunoregulatory effects of morphine on human lymphocytes.Clin Diagn Lab Immunol. 1997; 4: 127-132Crossref PubMed Scopus (95) Google Scholar reported that morphine could modulate mice T-helper cell differentiating in vitro, resulting in the rise of Th2 subsets that suppressed cell-mediated immunity. Our results provided evidence that both morphine and tramadol could direct human T-helper cell into Th2 and the effect of morphine was apparently more powerful than tramadol. Both drugs showed a dose-dependent Th2 differentiation response. T-helper cell differentiation is controlled by a number of factors. Th2 differentiation directed by morphine or tramadol was closely associated with the levels of corresponding cytokines, which was the cause of the immune alteration. To summarize, our research indicated that after pretreatment with morphine or tramadol in vitro, human T-helper cells tended to differentiate into Th2 cells.