MELATONIN AS BIOLOGICAL RESPONSE MODIFIER IN CANCER-PATIENTS

The neuroendocrine system modulates the immune response through neurop eptides and neurohormones, findings which point to the existence of a neuro-endocrine-immune system regulatory axis. At the same time, there is growing evidence that the pineal gland has anti-neoplastic propert ies, which include the action of its principal hormone, melatonin (MLT ) on the immune system through the release of cytokines by activated T -cells and monocytes. The present study was carried out on 3l patients (19 males and 12 females age range 46-73 years) with advanced solid t umors (7 gastric, 9 enteric, 8 renal, 5 bladder, 2 prostate) who eithe r failed to respond to chemotherapy and radiotherapy or showed insigni ficant responses and were therefore shifted to MLT therapy (10 mg/die orally for 3 months). We obtained blood samples just before the start of MLT administration and after 30 days of therapy. Plasma was collect ed in EDTA tubes on ice, immediately centrifuged at 4 degrees C and st ored frozen at -80 degrees C; samples were measured by immunoradiometr ic assays (Medgenix - Fleurus, Belgium) for tumor necrosis factor alph a (TNF) interleukin-1, 2 and 6 (IL-1, IL-2, IL-6) and interferon gamma (IFN). We used Student's paired t-test to compare each patient's cyto kine circulating levels before and after MLT administration and found a significant differences (p < 0.05). After 3 months of therapy, none of our patients displayed adverse reactions to MLT or had to discontin ue treatment. Nineteen patients (61%) showed disease progression. The other 12 (39%), however, achieved disease stabilization with no furthe r growth of either the primary tumor or of secondaries; moreover, they experienced an improvement in their general well-being, in terms of T chekmedyian's criteria, associated with a significative decrease of IL -6 circulating levels. These findings are consistent with the hypothes is that MLT modulates immune function in cancer patients by activating the cytokine system which exerts growth-inhibitory properties over a wide range of tumor cell types. Furthermore, by stimulating the cytoto xic activity of macrophages and monocytes, MLT plays a critical role i n host defence againist the progression of neoplasia.