Abstract
BackgroundThe 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 mantain 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. MethodsIn 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.ResultsA 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, CD8bright, CD8dim, CD16, TcRδ1 and δTcS1 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, CD8bright, TcRδ1 and δTcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients.ConclusionThe 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
Highlights
The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors
All samples were analyzed in duplicate in a single assay; the intrassay and interassay coefficients of variation were below 13% and 16% respectively for melatonin, 10% and 9% for cortisol, 5% and 6% for thyrotropin-releasing hormone (TRH), 8% and 7% for thyroid-stimulating hormone (TSH), 4% and 6% for FT4, 5% and 3% for growth hormone (GH), 3% and 8% for insulin like growth factor (IGF)-1, 5% and 7% for IL-2
Analyses of lymphocyte subpopulations were performed on unfixed cell preparations with a fluorescence activated cell sorter (FACScan, Becton-Dickinson FACS Systems, Sunnyvale, California) and a panel of monoclonal antibodies to lymphocyte surface antigens (Ortho Diagnostic Systems: OKT3, OKT4, OKT8, OK-NK, OKB20, OKT26a, OK-DR; Thermo-Scientific, Rockford, IL, USA: TcRδ1 and δTcS1). mAbs were directly conjugated with phycoerythrin (PE) and to fluorescein isothiocyanate (FITC). 10 μl mAbs were added to 100 ml ethylenediamine tetraacetic acid (EDTA) blood in Trucount tubes (BD Biosciences, San Jose, CA)
Summary
The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. 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. There are close relations between endocrine, nervous and immune system. Cortisol has a well recognized influence on immune function, inducing significant immunosuppression, characterized by the reduced cellular and humoral response of monocytes and B and T lympho-. Recent studies have put in evidence that growth hormone (GH) and IGF-1 have an important role in stimulating lymphocyte production and function [9]. The purpose of this study was to evaluate the 24-hour profiles of lymphocyte subsets and neuroendocrine hormones with the aim to highlight alterations in patients suffering from lung cancer
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