The interleukin-6 -174 G>C promoter polymorphism is associated with a higher risk of death after an acute coronary syndrome in male elderly patients.

Background: Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are key mediators of inflammation and their increased plasma levels are associated with acute coronary syndrome (ACS). Polymorphisms in the promoter region of IL-6 (-174 G>C) and TNF-alpha (-308 G>A) demonstrated to affect gene expression were analyzed to test their predictive power for cardiovascular death over one year follow-up in elderly male ACS patients.

Methods: We assessed the IL-6 -174 G>C polymorphism and TNF-alpha -308 G>A polymorphism in 139 consecutive elderly male patients affected by an ACS, such as ST-Elevation (STEMI), No ST-Elevation (NSTEMI) Myocardial Infarction and Unstable Angina.

Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice.

Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER-2/neu in tumoral mammary glands from Res-treated mice and in tumor cell lines.

The -174 C/G locus affects in vitro/in vivo IL-6 production during aging.

IL-6 in vitro production, as well as the serum/plasma concentration of the cytokine, increase with age. In the present investigation, a total of 62 individuals (31 males and 31 females), aged from 29 to 93 years of age (mean age of males: 60.4 years; mean age of females: 59.

The endocrinology of aging and its relationship to space physiology.

During the last century the number of people over 65 years of age has increased more than four-fold in the industrialized countries and by the year 2030 might account for 20% of the population. Life expectancy at birth is now about 75 (vs. 47 in 1900) and at 75 is 86 years.

Different age-related effects of thymectomy in myasthenia gravis: role of thymoma, zinc, thymulin, IL-2 and IL-6.

Different age-related immune pathogenetic mechanisms in myasthenia gravis (MG) have been suggested because of restoration after thymectomy (Tx) of altered zinc, thymulin (TH) and T-cell subsets exclusively in early-onset patients (younger <50 years), not in late-onset patients (older >50 years). In this context interleukin-2 (IL-2), interleukin-6 (IL-6) and thymoma are crucial because both involved in MG pathogenesis and correlated with acetylcholine receptors (AchRs) Ab production. Moreover, IL-2 and IL-6 are zinc-dependent, are altered in aging and related with zinc and TH age-dependent declines.

Generation of human lymphokine-activated killer cells following an IL-2 pulse in elderly cancer patients.

The toxicity of high-dose interleukin 2 (IL-2) treatments limits its use in tumour therapies, particularly in older age groups, characterized by a reduced tolerance to antineoplastic therapies. Here, we evaluated the possibility to induce cytotoxic lymphokine-activated killer (LAK) cells through a brief exposure (1-h pulse) of peripheral blood mononuclear cells (PBMC) from elderly cancer patients to high concentrations of IL-2. The cytotoxic activity, phenotype, apoptosis, and cell cycle phase of IL-2 pulsed PBMC were determined and compared with those of non-pulsed PBMC cultured continuously in IL-2.

Thyroid and thymic endocrine function and survival in severely traumatized patients with or without head injury.

Objective: Functional links among the brain, endocrine and immune system have been described previously. An impairment of both immunological defence mechanisms and thyroid hormone turnover was present in trauma conditions. An investigation on the relevance of thymulin and thyroid hormones in multiple trauma patients with or without head injury has been performed.

Evaluation of lymphokine-activated killer cell development in young and old healthy humans.

The kinetics of the development of lymphokine-activated killer (LAK) cell activity, the surface phenotype, and the expression of p55 and p75 interleukin 2 receptors (IL-2R) on IL-2-activated peripheral lymphocytes have been investigated in young and old healthy humans selected according to the Senieur Protocol criteria. No difference is present between young and old healthy subjects in terms of LAK cell activity development. The proliferative capacity of lymphocytes incubated with IL-2 shows similar kinetics in young and old subjects.

Pituitary-thyroid axis and immune system: a reciprocal neuroendocrine-immune interaction.

A good body of experimental and clinical results has supported the existence of numerous reciprocal interactions among the nervous, endocrine and immune systems. Increasing evidence has been accumulated in the last years on the interaction between pituitary-thyroid hormones and the immune system on the basis of either the existence of receptors for thyreotropic and thyroid hormones on lymphocytes or the frequent immune alteration in physiological and pathological fluctuations of thyroid hormones. The data were obtained either in animals with experimentally induced hyper- or hypothyroidism or in humans with various hyperthyroid or hypothyroid situations.

Plasma zinc level and thymic hormone activity in young cancer patients.

It has been reported that in many neoplastic diseases, including leukemia, alterations in plasma zinc levels may frequently occur, although the causes for such alterations have yet to be clearly defined. Since zinc is required to induce biological activity to thymulin (Zn-FTS), a biochemical defined thymic hormone, and marginal zinc deficiencies may prevent its peripheral biological activation, we investigated the plasma level of zinc and of both active thymulin (Zn-FTS) and total zinc saturable thymulin (Zn-FTS + FTS) in 91 young patients affected by acute lymphoblastic leukemia (ALL) at various stages of the disease. It was discovered that the plasma zinc level was reduced at the onset and relapse, whereas in complete remission and in off-therapy it was in the normal range.

Biomarkers of aging in the neuroendocrine-immune domain. Time for a new theory of aging?

A common and generally accepted assumption is that with advancing age, the thymus undergoes progressive and irreversible involution. This is considered the main cause for the age-related deterioration of various immune functions and, ultimately, for the increased incidence of infectious, neoplastic, and automimmune diseases in old age. This assumption is no longer tenable because of several clear-cut demonstrations that age-related thymic involution is not an intrinsic and irreversible phenomenon.

Cholesterol-rich rabbit serum modulates beta-adrenergic receptor density of human lymphocytes. A possible role of LDL-cholesterol.

The effect of in vitro treatment of human lymphocytes with rabbit cholesterol-rich serum (RCS) on the membrane microviscosity as well as on the beta-adrenergic receptor density has been investigated. RCS treatment of cells resulted in a 30% decrease of receptor density without any effect on membrane microviscosity. A complete recovery was observed incubating the RCS cells either with the "Active Lipids" (AL) or with heparin.

Age-related alterations of isoproterenol-stimulated adenylyl-cyclase activity are partially corrected by thymic graft.

Previous experimental results have demonstrated progressive impairments in beta-adrenergic responsiveness with advancing age. Beta-adrenoceptors are involved in the alterations as their density progressively decreases during aging. Alterations in both in vivo responsiveness and receptor density are corrected by neonatal thymic grafts.

In vitro restoration by thymulin of NK activity of cells from old mice.

Old mice show a reduced natural killer (NK) cell activity. Among the causes proposed to explain this defect, both intrinsic failure of NK cells or age-related alteration of microenvironmental factors relevant for NK function, have been taken into consideration. The findings reported in the present paper, demonstrate that thymic peptides, and in particular the facteur timique serique (FTS), more recently called thymulin (ZnFTS) in its zinc-bound form, whose production and activity is generally reduced in old age, is able, when administered in vitro, to restore the crippled NK cytotoxicity of spleen cells from old mice.