Melatonin, Sleep, and Immune Modulation: Role in Health and Disease

Abstract

Sleep and the immune system share regulatory molecules. These molecules, mostly cytokines, are involved in both physiological sleep and the disturbed sleep observed during infection. It is feasible that sleep influences the immune system through the action of centrally produced cytokines that are regulated during sleep (see, for example, ref. [2]). In humans, both sleep and the neuroendocrine-immune system are controlled by a double-command system given by predictive and reactive homeostasis processes. Predictive homeostasis is the primary role of the circadian system. Pineal melatonin is a major circadian signal released to circulation daily at night. In all mammals, circulating melatonin is synthesized primarily in the pineal gland and constitutes the chemical code of night. Thus, many of the reported effects of melatonin on the immune system may depend on melatonin's role in sleep. In addition, melatoin is also locally found in various cells, tissues, and organs including lymphocytes, human and murine bone marrow, the thymus, the gastrointestinal tract, skin, and the eyes, where it plays either an autocrine or paracrine role. Melatonin is a powerful antioxidant that scavenges superoxide radials as well as other radicar oxygen and nitrogen species and gives rise to a cascade of metabolites sharing its antioxidant properties. The antioxidant effect of melatonin is also exerted indirectly via promotion of gene expression of antioxidant enzimes and inhibition of gene expression of prooxidant enzimes. The objective of the review is to summarize some of the mechanisms implicatd in the mutual interaction among sleep, melatonin, and the immune system