Normalization of the light/dark rhythm of melatonin after prolonged subcutaneous administration of interleukin‐2 in advanced small cell lung cancer patients

It has been demonstrated that antitumor immune response is an IL‐2‐dependent phenomenon. Moreover, experimental results suggest the existence of interactions between IL‐2 and the pineal gland, which also plays a role in the control of immunity and cancer growth. Alterations of both IL‐2 and melatonin secretion have been reported in cancer patients. To further investigate pineal/IL‐2 relationships in humans with cancer, we evaluated the melatonin rhythm in seven advanced small cell lung cancer patients, before and at weekly intervals during immunotherapy with IL‐2, given subcutaneously at a daily dose of 3 × 106 IU/m2 twice daily for 5 days/week for 4 weeks. Before IL‐2, no patient showed a light/dark rhythm of melatonin. IL‐2 administration induced a normalization of the melatonin circadian rhythm, with the appearance of a night time peak in 4/7 patients. This effect, however, disappeared with IL‐2 interruption in 3/4 patients. This preliminary study, by showing that IL‐2 may restore a normal melatonin rhythm, suggests that the anomalous pineal function in cancer may depend at least in part on the altered endogenous IL‐2 production