Melatonin counteracts the immunosuppressive effect of serum from stressed mice on lymphocyte proliferation

The pineal neurohormone, melatonin (MLT), exerts an important immunoregulation on the mammalian immune system. We found that exogenous MLT counteracts the immunosuppressive effect of serum from mice subjected to physical restraint. In the experiment, phosphate buffered saline (PBS) control, PBS stress, MLT control and MLT stress groups were tested. Mice from MLT stress group were injected with MLT (12.5～50mg/kg, i.p.) for 2 days. On the 2nd day, after MLT injection, the mice were stressed by continued restraint for 16 hours as did before. Serum samples were tested for their immunosuppressive effect on normal lymphocyte transformation. The results showed that the lymphocyte transformation (counts/min) in PBS stress group was inhibited ( P 0.01 vs PBS control, ANOVA); whereas in MLT stress group, the cpm was significantly higher than in PBS stress group ( P 0.01, ANOVA), but MLT itself did not increase counts/min of normal lymphocyte transformation as showed in MLT control group and in vitro lymphocyte culture. Moreover, MLT could counteract the suppressive effect of stressed serum in a dose dependent manner. As shown by in vitro test, the possibility of MLT functioned with a physiological mechanism and functioned at the target cell (lymphocyte) level was ruled out. In conclusion: MLT could counteract the immunosuppressive effect of stressed serum with a pharmacological mechanism, which may happen in the early stage of restraint stress.