Psychoneuroendocrine modulation of regulatory T lymphocyte system: in vivo and in vitro effects of the pineal immunomodulating hormone melatonin.
BACKGROUND
At present, it is known that cancer-related immunosuppression would mainly depend on an immunosuppressive action mediated by a subtype of CD4+ lymphocytes, the so-called regulatory T lymphocytes (T-reg), which are identified as CD4+CD25+ cells. Moreover, it has been shown that anticancer immunity is under psychoneuroendocrine regulation, mainly mediated by the pineal hormone melatonin (MLT). This study was performed to investigate the in vivo and in vitro effects of MLT on T-reg generation.


METHODS
We evaluated the in vivo effects of MLT (20 mg/daily orally in the evening) in 20 patients with untreatable metastatic solid tumor and the in vitro effects of MLT incubation (at 10 and 100 pg/ml) of pure lymphocyte cultures on T-reg cell count.


RESULTS
MLT induced a statistically significant decline in mean T-reg cell numbers in patients who achieved disease control, whereas no effect was seen in those who had progressed. In contrast, no in vitro effect of MLT incubation was apparent.


CONCLUSIONS
This preliminary study would suggest that MLT may exert in vivo an inhibitory action on T-reg cell generation in cancer patients which is associated with a control of the neoplastic progression, whereas no direct effect was seen in vitro on lymphocyte differentiation. This finding would suggest that MLT may counteract T-reg cell generation in vivo by inhibiting macrophage activity which is involved in stimulating T-reg cell production.
Laboratory of Immunomicrobiology, S. Gerardo Hospital, Monza, Milan, Italy.
Luigi
L
Vigoré
Giusy
G
Messina
Fernando
F
Brivio
Luca
L
Fumagalli
Franco
F
Rovelli
Giuseppe
G
DI Fede
Paolo
P
Lissoni
D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000276:immunology; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000276:immunology; D010166:Palliative Care / Q000379:methods; D010865:Pilot Projects; D010870:Pineal Gland / Q000276:immunology; D011598:Psychoneuroimmunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D007155:Immunologic Factors; D008550:Melatonin