Immunomodulatory properties of a pineal indole hormone other than melatonin, the 5-methoxytryptophol

Several experiments have suggested that the pineal gland has an antitumor immunomodulatory action. Melatonin (MLT), the best known pineal hormone, has been shown to stimulate anticancer immune defenses during the night, corresponding to the period of its maximum blood levels, whereas it has no effect during the light phase of the day. At present, no study has been performed to investigate possible immunomodulating properties of other pineal indoles, such as 5-methoxytryptophol (5-MTL), whose circadian secretion would be opposite with respect to that of MLT, since it reaches its highest levels during the light phase of the day. In an attempt to analyze possible effects of 5-MTL on anticancer immunity, we have evaluated the action of 5-MTL (1 mg/ day orally at noon for 5 days) in 10 healthy volunteers on the two fundamental suppressive and immunostimulatory cytokines, consisting of IL-6 and IL-2, respectively. Serum levels of IL-2 and IL-6 were measured by an immunoradiometric method. Mean serum concentrations of IL-2 significantly increased on 5-MTL therapy, whereas those of IL-6 significantly decreased in response to 5-MTL. This preliminary study would suggest that the less known pineal indole 5-MTL, as well as MLT, has important immunomodulatory effects on cytokine secretions, including those involved in the antitumor immune response, by further confirming the essential role of the pineal as a central regulation of biological response modifier system. Several pineal alterations have been described in advanced cancer patients. According to the results of this study, the simultaneous administration of MLT during the dark phase and of 5-MTL during the light period of the day could further contribute to correcting pineal functions and to pilot the host anticancer immune reaction in an antitumor direction with respect to MLT alone.