Melatonin as a therapeutic agent in experimental endotoxic shock

We demonstrated that the pineal neurohormone melatonin exerts immunoregulatory effects via T-helper 2 (Th2) cell products. Th2 products may modulate the secretion and/or action of inflammatory cytokines, which play an important role in the development of septic shock associated with endotoxemia. Here we report that a single melatonin injection protects mice treated with a lethal dose of lipolysaccharide (LPS) especially when melatonin was injected 3 to 6 hr after LPS. This effect did not apparently involve Th cells or inhibition of inflammatory cytokines or macrophage nitric oxide (NO) generation. Nevertheless, plasma nitrate concentration, which reflects the rate of NO synthesis, showed a significant reduction at 18 and 24 hr after LPS administration. Melatonin is being studied in humans for cancer immunotherapy. The data presented here identify melatonin as potential therapy for septic shock.