Modulation of cytokine production from TH2-lymphocytes and monocytes by the pineal neurohormone melatonin

Preliminary clinical and experimental studies have suggested that cytokine secretion is not regulated only by immune substances, but also by the neuroendocrine system through the release of immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). The anticancer immune response would also depend on complex interactions between cytokines and neurohormones. IL-2 is one of the most active antitumor cytokines. However, in addition to the generation of cytotoxic antitumor lymphocytes, IL-2 may concomitantly induce suppressive factors, in particular IL-10 by TH2 lymphocytes and IL-6 by both TH2 lymphocytes and monocytes. IL-10 appeared to inhibit IL-2 secretion and activity, whereas IL-6 has been proven to exert both antineoplastic and proneoplastic immune functions. The present experimental study was performed to evaluate the in vitro effects of MLT on IL-10 and IL-6 secretions, either in basal condition or after IL;2 stimulation. Human pure lymphocyte and pure monocyte cultures were obtained from healthy donors and incubated for 3 days with medium alone, MLT (100 pg/ml), IL-2 (100 Cetus U/ml) or IL-2 plus MLT. IL-2 induced a significant increase in mean medium concentrations of both IL-10 and IL-6. MLT alone had no effect on IL-10 levels, but it was able to significantly reduce IL-2-induced IL-10 release. IL-2-induced IL-6 secretion was not abrogated by a concomitant MLT incubation, whereas MLT alone was able to significantly reduce the basal secretion of IL-6 only in the pure monocyte cultures. These results, by showing a modulatory effect of MLT on lymphocyte and monocyte cytokine secretion, would further confirm the rationale of a concomitant administration of cytokines and immunomodulating neurohormones during cancer immunotherapies.