Research On The Effects And Mechanisms Of Daily Used Analgesia Agents

Backgroud Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures. One of the reasons associated with this immune dysfunction is the redirection of T cells toward Th2 differentiation. Recently more and more persons pay attention to ache after operation, and patient controlled analgesia(PCA) have widely used. The analgesia agents also play a role in this clinical problem but the mechanisms are not clear. Opioids, especially morphine, can affect immune function, but the effect and mechanisms of lately used new analgesia agents is not clear. Objective To observe the effect of different concentration of morphine, fentanyl, tramadol and lornoxicam on the differentiation of human helper T cells in vitro and study the mechanisms of anesthetics on cell-mediated immunosuppression. Methods Sixty out-patients without immune disease were selected andtheir peripheral blood was collected. Then the whole blood or peripheral blood mononuclear cells (PBMCs) were pretreated with different concentration of morphine, fentanyl, tramadol or lornoxicam for 24 hours, while the control group without any drugs. The level of CD4~+ IFN-γ~+ IL-2~+/ CD4~+IL-4~+IL-10~+ was analyzed by three-color flow cytometry. The intracellular cytokines after stimulation with PMA and Ionomycin were detected by trace whole blood technology. The CD4~+CCR5~+ and CD4~+ CCR3~+ cells in peripheral blood mononuclear cells (PBMCs) were counted to observe the imbalance of Thl/Th2. And the ABC-Elisa method was utilized to measure the levels of IFN-γ,IL-2,IL-4 and IL-10. Results After treatment with morphine, fentanyl, tramadol and lornoxicam, the number of Th2 increased significantly and the ratio of Th1/Th2 decreased dramatically in all groups. At the same time the number of IFN-γ~+IL-2~+ cells decreased and IL-4~+IL-10~+ cells increased sharply as compared with the control group. Compared different concentration in the same analgesia agent, with the concentration elevation, Th2 subsets obviously increased. The levels of cytokines in all drugs changed significantly, IFN-γ and IL-2 decreased, but IL-4 and IL-10 increased.Conclusion Morphine, fentanyl, tramadol and lornoxicam can direct Th0 cells toward Th2 differentiation, especially morphine and fentanyl. The Th2 redirection, as well as the changes in cytokine, showed a dosedependent fashion in all drugs.