Neuroendocrine-immune interactions in healthy aging.

AIM: The nervous, endocrine and immune systems are connected by shared neurotransmitters, hormones and cytokines. The function of these systems shows patterns of circadian rhythmicity and a number of age-related changes in the 24-h hormonal and non-hormonal rhythms have been found in older human beings. The aim of this study was to evaluate integration among the nervous, endocrine and immune systems in the elderly. METHODS: Cortisol and melatonin serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every 4 h for 24 h from 15 healthy young-middle-aged subjects (range 36-55 years, mean age±standard error [SE] 44.08±1.76) and 15 healthy old-aged subjects (range 67-79 years, mean age±SE 68.52±1.27). RESULTS: There was a statistically significant difference between the groups in the observed values of CD20 (total B cells higher in young-middle-aged subjects, P=0.02), CD25 (activated T cells with expression of the α-chain of interleukin-2 receptor, higher in elderly subjects, P=0.04) and DR+ T cells (activated T cells higher in elderly subjects, P=0.01). There were different correlations among lymphocyte subpopulations and hormone serum levels in young and middle-aged subjects in compared to old-aged subjects. In the group of young-middle-aged subjects, a clear circadian rhythm was validated for the time-qualified changes of all the factors studied. In the group of elderly subjects, a clear circadian rhythm was validated for the nyctohemeral changes of CD3 (with a phase delay of 3 h), CD8, CD4/CD8 ratio, CD16, CD25 (in opposite phase), cortisol (with a phase delay of 1 h) and melatonin. CONCLUSION: The results of the current study show that aging is associated with enhanced responsiveness of the T-cell compartment, impairment of B-cell compartment and alterations in temporal architecture and correlations of neuroendocrine-immune parameters.

A possible mechanism for altered immune response in the elderly.

BACKGROUND: Reciprocal influences and bidirectional connections among the nervous, endocrine and immune systems, mediated by shared neuroendocrine hormones, chemo/cytokines and binding sites contribute to the maintainment of body homeostasis. The hypothalamus-pituitary axis may play an immunomodulating role and influence cellular immune responses by releasing various hormones and neuropeptides into the blood with direct modulatory action on the immune effectors, or by regulating the hormonal secretion of peripheral endocrine glands. Aging is associated with changes in immune function. The aim of this study was to evaluate circadian variations of some endocrine and immune factors in the elderly. MATERIALS AND METHODS: Serum levels of cortisol, melatonin, thyrotropin-releasing hormone (TRH), thyroid stimulating hormone (TSH), free thyroxine (FT(4)), growth hormone (GH), insulin-like growth factor (IGF) 1 and interleukin (IL) 2 were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from ten healthy young and middle-aged individuals (age 35-54 years) and from ten healthy elderly individuals (age 65-76 years). RESULTS: There was a statistically significant difference between the groups in the observed values of CD20 and TSH serum levels (higher in the young and middle-aged) and CD25 and DR(+) T-cells (higher in the elderly). In the group of young and middle aged subjects, a clear circadian rhythm was validated for the time-qualified changes of all the factors studied, with the exception of FT(4), IGF1 and IL2. In the group of elderly individuals, a number of rhythms and correlations with neuroendocrine hormones were absent or altered. CONCLUSION: The results of the current study evidence aging-associated decrease of peripheral B-cell compartment, increase of activated T-cell compartment, decrease of hypophyseal thyrotropin secretion, altered circadian rhythmicity and altered hormone-immune cell correlations.

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. CONCLUSION: 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.

Aging related changes of circadian rhythmicity of cytotoxic lymphocyte subpopulations.

BACKGROUND: Immunosenescence is a process that affects all cell compartments of the immune system and the contribution of the immune system to healthy aging and longevity is still an open question. Lymphocyte subpopulations present different patterns of circadian variation and in the elderly alteration of circadian rhythmicity has been evidenced. The aim of our study was to analyze the dynamics of variation of specific cytotoxic lymphocyte subsets in old aged subjects. METHODS: Lymphocyte subpopulation analyses were performed and cortisol serum levels were measured on blood samples collected every four hours for 24 hours from fifteen healthy male young-middle aged subjects (age range 36-55 years) and fifteen healthy male old aged subjects (age range 67-79 years). RESULTS: In healthy young-middle aged subjects CD20 were higher and at 06:00 h CD8+ dim correlated positively with CD16+ and positively with gammadeltaTCR+ cells, CD16 correlated positively with gammadeltaTCR+ cells At 18:00 h CD8+ dim correlated positively with CD16+ and positively with gammadeltaTCR+ cells, CD16+ correlated positively with gammadeltaTCR+ cells and a clear circadian rhythm was validated for the time-qualified changes of CD3+, CD4+, CD20+, CD25+ and HLA-DR+ cells with acrophase during the night and for the time-qualified changes of CD8+, CD8+ bright, CD8+ dim, CD16+ and gammadeltaTCR+ cells with acrophase during the day. In old aged subjects CD25, DR+ T cells and cortisol serum levels were higher, but there was no statistically significant correlation among lymphocyte subpopulations and a clear circadian rhythm was evidenced for time-qualified changes of CD3+ and CD25+ cells with acrophase during the night and for the time-qualified changes of CD8+ cells and cortisol with acrophase during the day. CONCLUSION: Our study has evidenced aging-related changes of correlation and circadian rhythmicity of variation of cytotoxic lymphocyte subpopulations that might play a role in the alteration of immune system function in the elderly.

Melatonin and cortisol serum levels in lung cancer patients at different stages of disease.

BACKGROUND: Numerous interactions exist among the nervous, endocrine, and immune systems, mediated by neurotransmitters, hormones, and cytokines. Melatonin may modulate the integrated functions of a unique neuro-immune-endocrine system. Neoplastic diseases may be linked to progressive loss of integration among these systems. We investigated whether there are differences among healthy elderly people and elderly people suffering from lung cancer at different stages of disease in 24-hour melatonin and cortisol secretory profiles. MATERIAL/METHODS: In seventeen healthy subjects (mean age +/-S.E.: 68.8+/-1.92 years), seventeen patients with stage I and II lung cancer (mean age: 67.2+/-0.80), seventeen patients with stage III and IV lung cancer (mean age: 69.5+/-2.26), melatonin and cortisol serum levels were measured in blood samples collected every four hours for 24 hours. The area under the curve (AUC) and the presence of circadian rhythmicity were evaluated. RESULTS: The circadian rhythm of melatonin was present in all the groups, but serum levels were decreased in the subjects suffering from lung cancer (P<0.05). In these patients, cortisol serum levels were increased (not in a significant way), with a loss of the circadian rhythm of secretion. The melatonin/cortisol ratio was decreased in stage III and IV cancer patients (P<0.05). CONCLUSIONS: The progressive decrease of melatonin secretion and altered cortisol secretion pattern with advancing stage of neoplastic disease may be an expression of a gradual alteration of the integrated function of the neuro-endocrine system in lung cancer patients.

Neuroendocrine alterations in lung cancer patients.

BACKGROUND: A number of qualitative and quantitative changes in hormonal secretion pattern have been found in subjects suffering from neoplastic disease. The aim of this study was to evaluate the presence of alterations in neuro-endocrine system function and in the pattern of endocrine secretion in patients with lung cancer. METHODS: Cortisol, melatonin, growth hormone (GH), insulin-like growth factor I (IGF-I), thyrotropin-releasing hormone (TRH), thyroid-stimulating-hormone (TSH), and free thyroxine (FT4) serum levels were measured on blood samples collected every four hours for 24 hours from ten healthy old subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve and mean diurnal and nocturnal levels were compared and the presence of circadian rhythmicity was evaluated. RESULTS: When hormone levels were expressed as area under the curve GH levels were higher (p=0.004) and IGF-I levels were lower (p=0.006) in patients with lung cancer than in normal subjects. The evaluation of melatonin/cortisol ratio in all subjects showed a significant difference between the control group and the group of cancer patients (p<0.05). When we compared mean diurnal levels (mean of 06.00-10.00-14.00h) GH levels were higher (p<0.0001) and IGF I levels were lower (p<0.0001) in cancer patients; when we compared mean nocturnal levels (mean of 18.00-22.00-02.00h) cortisol (p=0.03), TRH (p=0.02), and GH (p=0.001) levels were higher in cancer patients, while melatonin (p=0.04), TSH (p=0.04) and IGF I (p<0.0001) levels were higher in control subjects. A clear circadian rhythm was validated for time related changes of cortisol, melatonin, TRH, TSH and GH in control subjects and for time related changes of melatonin in cancer patients. CONCLUSION: These data suggest that lung cancer patients show alterations of hormone secretion and neuroendocrine system function.

[Interstitial lung diseases]. / Pneumopatie interstiziali.

Interstitial lung diseases (ILD) are an heterogeneous group of inflammatory diseases characterized by an anatomical distortion of peripheral airways and interstitium, determined by a first stage of alveolitis and a following stage of fibrosis. Natural history of several ILD is characterized by slow and progressive destruction of alveolar-capillary functional units, often with respiratory failure and death. For their smoldering evolution and not specificity of symptoms (exertional dyspnea and cough) ILD may remain not diagnosed and not treated for a long time.

[Melatonin in the international literature of the last twenty years]. / La melatonina nella letteratura internazionale dell'ultimo ventennio.

Melatonin was not considered for a long time in medical culture and scientific research for the difficulties encountered in study protocols and for the obscure relevance in clinical practice. Today the pineal hormone has reached a great popularity, may be not strictly corresponding to the important role played in the regulation of many system function and the commercial diffusion has become extremely wide in some countries.

[Non-invasive hemodynamic assessment with bioimpedance in patients with subclinical hypothyroidism before and after treatment with levo-thyroxin]. / Valutazione emodinamica non invasiva mediante bioimpedenziometria in pazienti con ipotiroidismo sub-clinico prima e dopo trattamento con levo-tiroxina.

Subclinical hypothyroidism is characterized by normal serum levels of free thyroxine and triiodothyronine with increased serum levels of thyroid-stimulating hormone (TSH) without symptoms. We evaluated by thoracic electrical bioimpedance cardiography the hemodynamic pattern of 38 patients with subclinical hypothyroidism, before and after 6-month therapy with levo(L)-thyroxine. We have not evidenced statistically significant differences for cardiac index, cardiac frequency and vascular peripheral resistances. TSH levels were decreased in a statistically significant way. Results obtained in our study show that hemodynamic pattern is not changed after hormone therapy in patients affected by subclinical hypothyroidism.

[Cardiac metastasis of poorly differentiated adenocarcinoma of unknown primary site]. / Metastasi cardiache di adenocarcinoma poco differenziato a sede primitiva occulta.

The finding of intracardiac masses is very uncommon. In this patient the early clinical picture was characterized by neurologic signs and symptoms as mild forgetfulness, blurred vision, a sensation of imbalance, anorexia, weight loss. Brain magnetic resonance imaging showed multiple metastatic lesions, computed tomography of the chest, abdomen and pelvis showed intraatrial masses and whole body nuclear scanning evidenced bone lesion. It was not possible to find the primary tumor by other instrumental or laboratory exams. Transesophageal echocardiography showed a mass originating from interatrial septum, with atrial invasion and risk of embolization from the left atrium. The patient was transferred to the operating room for cardiac surgery, the mass at risk for embolization was resected and the specimen consisted of fibrous and fibrino-necrotic tissue infiltrated by poorly differentiated adenocarcinoma. The patient received brain and bone radiotherapy and chemotherapy with cisplatin and vinorelbin.