Altered time structure of neuro-endocrine-immune system function in lung cancer patients.
BACKGROUND
The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. The nervous, endocrine and immune system might act as an integrated unit to maintain body defense against this pathological process and reciprocal influences have been evidenced among hypothalamus, pituitary, thyroid, adrenal, pineal gland and immune system. In this study we evaluated differences among healthy subjects and subjects suffering from lung cancer in the 24-hour secretory profile of melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 and circadian variations of lymphocyte subpopulations.


METHODS
In ten healthy male volunteers (age range 45-66) and ten male patients with untreated non small cell lung cancer (age range 46-65) we measured melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 serum levels and percentages of lymphocyte subpopulations on blood samples collected every four hours for 24 hours. One-way ANOVA between the timepoints for each variable and each group was performed to look for a time-effect, the presence of circadian rhythmicity was evaluated, MESOR, amplitude and acrophase values, mean diurnal levels and mean nocturnal levels were compared.


RESULTS
A clear circadian rhythm was validated in the control group for hormone serum level and for lymphocyte subsets variation. Melatonin, TRH, TSH, GH, CD3, CD4, HLA-DR, CD20 and CD25 expressing cells presented circadian rhythmicity with acrophase during the night. Cortisol, CD8, CD8(bright), CD8(dim), CD16, TcRdelta1 and deltaTcS1 presented circadian rhythmicity with acrophase in the morning/at noon. FT4, IGF-1 and IL-2 variation did not show circadian rhythmicity. In lung cancer patients cortisol, TRH, TSH and GH serum level and all the lymphocyte subsubsets variation (except for CD4) showed loss of circadian rhythmicity. MESOR of cortisol, TRH, GH, IL-2 and CD16 was increased, whereas MESOR of TSH, IGF-1, CD8, CD8(bright), TcRdelta1 and deltaTcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients.


CONCLUSIONS
The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system.
Mazzoccoli
Gianluigi
G
Unit of Internal Medicine, IRCCS Scientific Institute and Regional General Hospital, Casa Sollievo della Sofferenza, Opera di Padre Pio da Pietrelcina S. Giovanni Rotondo (FG), Italy. g.mazzoccoli@tin.it
Vendemiale
Gianluigi
G
De Cata
Angelo
A
Carughi
Stefano
S
Tarquini
Roberto
R
D000368:Aged; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000502:physiology*; D004703:Endocrine System / Q000503:physiopathology*; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015213:Neuroimmunomodulation; D009490:Neurosecretory Systems / Q000503:physiopathology*; D013997:Time Factors