The in vivo effect of melatonin on cellular activation processes in human blood during strenuous physical exercise

Melatonin has been reported to have anti- as well as pro-inflammatory properties. Because physical stress is associated with the activation of blood cells, the present study examines melatonin's role in exercise-induced cell activation processes. Eight healthy volunteers (aged 20-62 yr, mean = 31), exercised on an 'Ergometric' bike for 30 min at 80% of their calculated maximum pulse rate. Blood samples were taken just before melatonin administration, directly after exercise, and 2 hr after exercise completion. Cytokine and eicosanoid parameters were measured in plasma from blood stimulated with lipopolysaccharide (LPS) for 2 hr whereas tissue factor (TF) activity was measured in isolated monocytes. Melatonin significantly decreased LPS-induced TF activity by 48% (P < 0.01) directly after exercise, and a 44% reduction was seen 2 hr later (P < 0.02). Furthermore, melatonin significantly reduced the lymphocyte count rise produced directly after exercising by more than 30% (P < 0.01). A trend was also seen for melatonin suppressing the increase of WBC by around 10% and to strengthen the platelet increase by about 8% after physical stress. Melatonin also significantly lowered RBC and hemoglobin counts by 5 and 3-4% during exercise (P < 0.005 and <0.02 respectively). Two hours after exercise, melatonin tended to lower leukotriene B4 levels by 30%. Interleukin-8 and tumor necrosis factor-alpha levels tended to be lower in individuals who had taken melatonin following hard physical activity and a larger sample size may show significance. Thromboxane B2 production seemed unaffected by melatonin during exercise. In conclusion, in vivo intake of melatonin appears to suppress LPS-induced activation of monocytes in whole blood reactions associated with physical exercise and facilitates the down-regulation of inflammatory mediators.