Endocrine effects of a 24-hour intravenous infusion of interleukin-2 in the immunotherapy of cancer.

Several experiments have demonstrated that there is a relationship between neuroendocrine and immune systems. Despite these interesting findings, only few studies have been performed up to now to evaluate the possible importance of neuroimmune interactions in influencing the biological efficacy and toxicity of cancer immunotherapy with IL-2. To analyze the effects of IL-2 on endocrine secretions, we have measured by RIA serum levels of cortisol, beta-endorphin, GH, PRL and of the pineal hormone melatonin in metastatic renal cancer patients, treated with 5-day courses of IL-2 at a daily dose of 3 x 10(6) U/m2, given through a 24-hour intravenous infusion. Six IL-2 courses were evaluated, by collecting blood samples at 4-hour intervals for 24 hours and by comparing the hormonal values with those observed in baseline conditions. Both cortisol and beta-endorphin mean values significantly increased during IL-2 infusion. GH and PRL also increased, but not in a significant manner. Finally, melatonin mean levels significantly decreased during the infusion. The IL-2-induced effects on cortisol, beta-endorphin and melatonin resulted in a complete abolition of their physiological circadian rhythm. These results show that IL-2 infusion induces important changes in endocrine secretions. Because of the immunosuppressive effect of cortisol and the stimulatory one of melatonin, their changes during IL-2 infusion might influence the biological activity of immunotherapy itself. Further studies will be required to define better the clinical importance of IL-2 induced hormonal changes.