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A Study on the Endocrine Function of Pineal Gland with Regard To Immune Alterations in Cancer Patients

Paolo Lissoni, Vichy Cenaj, Franco Rovelli, Giusy Messina, Giorgio Porro, Fernando Brivio and Giuseppe Di Fede

Several experimental studies have demonstrated that pineal gland plays a key anticancer role through the release of several hormones provided both by cytotoxic and immunostimulatory effects; the best-researched of all is melatonin (MLT). Despite the well documented anticancer role of the pineal gland, few clinical studies have been performed up to now in order to explore the pineal function in cancer patients. However, the results agree with the evidence of a progressive decline in the pineal function during the clinical course of neoplastic disease. Moreover, it is known that cancer progression is associated with a progressive decline in the effectiveness of anticancer immunity, which is mainly activated by lymphocytes and suppressed by monocyte-macrophage system, and which may be clinically investigated by evaluating the simple lymphocyte-to-monocyte ratio (LMR). So far, however, very few data about the possible relation between cancer-related immune and pineal alterations are available. The present study was carried out to evaluate the pineal function in a group of nonmetastatic and metastatic cancer patients in relation to the LMR values. The pineal function was investigated by measuring the light and dark urinary excretion of the main MLT metabolite, the 6-sulfatoxymelatonin (6-MTS). A normal light/dark rhythm in the circadian excretion of 6-MTS was present in the non-metastatic patients, whereas a loss of pineal rhythm occurred in the metastatic group. In the same way, a normal light/dark rhythm was present in the patients with normal LMR values, whereas no rhythm was observed in those with abnormally low LMR values. According to the results previously reported by other authors, this study confirms that the metastatic neoplastic disease is characterized by a loss of the light/dark rhythm in the pineal function. Moreover, by showing a relation between the loss of light/dark pineal rhythm and low LMR values, this study would suggest that cancer-related immune alterations may depend at least in part on the altered pineal function, because of the fundamental immunomodulatory role of pineal itself.