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

Abstract: 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