Numerous studies involving a definition of relationships between nervous, endocrine, and immune systems have
shown one of the most noteworthy discoveries in modern biology that these systems use a common chemical language
for intra- and intersystem communication (Fig. 1)[26]. In this framework, currently pineal-synthesized melatonin
is considered one of the members of the complex neuroendocrine-immunological network, and the existence of a bidirectional communication between the pineal gland and the immune system is accepted. In this context, a number of in vivo and in vitro studies have documented that melatonin plays a fundamental role in neuroimmunomodulation [17–19, 27, 28], and a direct correlation between melatonin production and the circadian and seasonal variations in the immune system has been documented [29, 30]. Reciprocally, immunological signals produced by the immunocompetent cells are perceived by the pineal gland and provide a feedback for the regulation of pineal function.