Neuroimmunotherapy with subcutaneous low-dose interleukin-2 plus the pineal oncostatic hormones melatonin and 5-methoxytryptamine in untreatable advanced solid neoplasm patients with very poor clinical status

Recent advances in knowledge of psychoneuroimmunity have shown that the bio logical activity of cytokines is under neuroendocrine regulatory control. O pioid peptides play a major immunosuppressive role, whereas the pineal horm ones stimulate host anticancer immune defenses. In particular, the pineal h ormone melatonin has been shown to amplify the anticancer efficacy of inter leukin-2 (IL-2) in human neoplasms. However it must be noted that melatonin is only one of the hormones produced by the pineal gland, even though only very preliminary data exist on the biological properties of pineal hormone s other than melatonin. Recent observations have shown that the pineal indo le 5-methoxytryptamine (5-MTT) may have greater oncostatic action in vitro than melatonin, however there are no data on the possible immunomodulating properties of 5-MTT at present. Our previous data had already shown that th e neuroimmune regimen with low-dose IL-2 plus melatonin was a well tolerate d and effective nsw anticancer schedule for advanced solid neoplasms resist ant to IL-2 alone. This preliminary phase II study was performed to investi gate the tolerability and the efficacy of a neuroimmune combination with IL -2, melatonin and the other pineal hormone, 5-MTT.