Aim. To summarize the present knowledge on functional connections between the pineal gland and immune system, with a special emphasis on the immunomodulatory effects of melatonin in humans.
Review. The pineal gland is a vertebrate neuroendocrine organ, transforming external photic signals into a biochemical message, comprehensible to all the cells of the organism. The signal is melatonin, synthesized and released into the bloodstream in a rhythmical manna, with a low level during the day and an increase at night. The same circadian rhythm of melatonin exists in all animals, irrespective of their circadian locomotor activity pattern. Melatonin is involved in the regulation of a majority of processes subject to circadian and seasonal rhythms, including body temperature and sleep in humans, breeding of wild-living animals, seasonal changes in their immune system activity, etc. Being a potent free-radical scavenger, it actively protects organisms against oxidative stress. Melatonin acts also on immune cells – directly, via specific receptors, and indirectly, through modification of the level and circadian rhythms of several other hormones involved in immunomodulation. Activated immune cells, in turn, synthesize and release the soluble message molecules, cytokines, influencing the biosynthesis of melatonin. Therefore, the pineal gland and melatonin are involved in the regulatory circuit composed of the nervous, endocrine and immune systems, responsible for the maintenance of homeostasis within the vertebrate organism.