A substance from pineal gland extracts, which lightens the skin melanocytes of amphibians and fishes, was isolated in 1958 and called melatonin (MLT, N-acetyl-5-methoxytryptamine).¹ In both diurnal and nocturnal species, the absence of light at night stimulates MLT biosynthesis. Electrical signals originating from the retina reach the suprachiasmatic nuclei which, in turn, send inputs via the paraventricular nuclei to the spinal cord and then to the superior cervical ganglia. The fibres terminate at the pinealocytes.² Absence of light results in increased norepinephrine release and activation of α1 and β-adrenergic receptors on the pinealocytes. This triggers a series of intracellular responses, resulting in activation of the enzymes N-acetyltransferase (EC 2.3.1.87) and hydroxyindole-O-methyl transferase (EC 2.1.1.4), which convert serotonin into MLT.² The circadian nocturnal release of MLT has a profound influence on the internal environment of the organism, with diverse physiological effects. The main function of MLT seems to be that of synchronising the organism in the photoperiod and it may have a role in reproduction, metabolism, seasonality, thermoregulation, and immunity.

MELATONIN AND THE HUMAN IMMUNE SYSTEM

Animal studies have shown that binding of MLT to specific receptors in antigen activated T helper (Th) cells results in an up regulation of cytokine production and immune function.³ In general, the immunoenhancing action of MLT seems restricted to T dependent antigens and to be most pronounced in immunodepressed situations. For example, MLT may completely counteract thymus involution and the immunological depression induced by stress or glucocorticoid treatment,⁴ or restore depressed immunological functions after soft tissue trauma and haemorrhagic shock.⁵ MLT may also rescue haematopoiesis in mice treated with cancer chemotherapeutic compounds.⁶ This effect apparently involves the endogenous release of granulocyte/macrophage colony stimulating factor and MLT-induced opioid cytokines.^3,6,7

The …