老年人长跑锻练后白细胞介素-1的变化及其和糖皮质激素受体的可能关系

本文研究长跑锻练对老年人血浆白细胞介素-1(IL-1)活性的影响及其和糖皮质激素受体(GR)的可能关系。IL-1活性用刺激C_(57)小鼠胸腺细胞增生后~3H-胸腺嘧啶核苷参入量的多少来表示,GR用~3H-地塞米松特异结合表示。结果表明:长跑锻练10年以上老年人(n=6)安静时血浆IL-1活性在14.7-18.7,3.8-7.0以及1.5-2.6KD之间出现三个淋巴细胞增生峰,分别为对照组老年人(n=4)的209％,223％和145％(P<0.05);而外周血白细胞GR水平较对照老年人降低,约为对照组的65％。本文对IL-1的活性和GR含量的关系和生理意义进行了讨论。     

Effects of exercise training on plasma cytokine and chemokine levels, and thermoregulation

Pyrogenic factors may include the proinflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and IL-8 (chemokine). Exercise also causes cytokinemia that might result in pyrogenically mediated body temperature elevation. The aim of the present study was to determine the effect of exercise training on exercise-induced plasma concentrations of IL-1β, IL-6, TNF-α, and IL-8. Messenger RNA levels of these factors were also evaluated in peripheral blood leukocytes. We also observed the relationship between cykokines, chemokines, and sweating after exercise. Nine tennis athletes (n=9) and untrained sedentary control subjects (n=10) ran for 1 h at 75% intensity of VO_2max. Venous blood samples were analyzed for plasma concentrations and mRNA expression in leukocytes of cytokines and chemokine of interest. Sweat volume was calculated by measuring body weight changes. Leukocyte mRNA expression and plasma protein levels of IL-1β, IL-6, TNF-α, and IL-8 immediately increased after exercise in both groups, but to a much greater extent in the athletic group. However, mRNA expression and plasma protein level for IL-6 and TNF-α, unlike IL-1β and IL-8, decreased more quickly in the athletic group compared to the control group during the recovery period. Compared to the control group, greater sweat loss volumes, and lower body temperatures in athletic group were observed at all time points. In conclusion, exercise training improved physical capacity and sweating function so that body temperature was more easily regulated during and after exercise. This may due to improved production of specific cytokine and chemokine in sweating during exercise.     

Granulocyte and plasma cytokine activity in acute cadmium intoxication in rats.

Changes in the number and ex vivo function of peripheral blood neutrophils were investigated following intraperitoneal administration of cadmium-chloride in rats. Besides a dose-dependent increase in the number of peripheral blood neutrophils, changes were found in the functional state of isolated polymorphonuclear leukocytes (PMNs). Increased spontaneous adhesion and activation, and TNF activity in a conditioned medium were observed in cultures of granulocytes in comparison to granulocytes from control (saline-treated) animals. Increased levels of plasma activity of inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were noted following cadmium administration. Cytological signs of pulmonary inflammation were revealed histologically and the majority of neutrophils recovered from the lungs by enzyme digestion exhibited a capacity of nitroblue tetrazolium (NBT) reduction. Our data demonstrate that acute cadmium intoxication leads to a systemic inflammatory response characterized by numerical and functional changes in the granulocyte compartment and to increased levels of inflammation-related cytokine activity in the circulation. Correlations between the increased number of peripheral blood neutrophils and IL-6 plasma activity (r=0.776, p<0.00001) and the number of neutrophils recovered from the lung tissue (r=0.893, p<0.00001) suggested that systemic cadmium-induced inflammation might be involved in the pulmonary toxicity of cadmium.     

Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6

Intermittent psychological stress was induced in adult rats by 2 h/day of immobilization stress for 4 days, with or without blocking the function of IL-6 by using an anti-IL-6 antibody. Basal concentrations of serum corticosterone, IL-1beta, IL-6, and TNF-alpha were assessed 24 h after the last intervention, as were levels of glucocorticoid receptors (GR) and activities of glucocorticoid-inducible enzymes (tyrosine aminotransferase and glutamine synthetase) in muscle and liver. Whole blood cultures were used to assess both spontaneous and LPS-induced reactivity of peripheral blood mononuclear cells. Stress increased corticosterone concentration in a manner partially modulated by IL-6. Serum IL-1beta concentration was downregulated during stress when IL-6 was blocked (P < 0.01). LPS-induced IL-6 secretion by peripheral blood mononuclear cells in vitro correlated positively with serum IL-1beta concentration in antibody-treated groups, independently of stress (R = 0.70 in nonstressed and R = 0.78 in stressed rats; both P < 0.05), whereas serum corticosterone concentration correlated positively with LPS-induced secretion of IL-6 only in control rats (R = 0.66; P < 0.05). Reductions in liver GR levels indicated independent effects of stress (34.5%) and anti-IL-6 antibody (16.7%) and additive effects for both (62.5%). Similar results are reported for vastus muscle. Conversely, stress increased tyrosine aminotransferase and glutamine synthetase activities in muscle and liver with a significant (P < 0.05) effect of anti-IL-6 antibody only seen in stressed livers. In conclusion, IL-6 plays a role in maintaining circulating IL-1beta concentration after multiple exposures to stress, thus promoting a continued elevation of corticosterone release; in peripheral tissues, IL-6 antagonizes the effects of glucocorticoids, especially at the level of GR concentration.     

Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors.

The objective was to determine the effects of exercise training on changes in blood immune function in postmenopausal breast cancer survivors. Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n=25) or control group (n=28). The exercise group trained on cycle ergometers three times per week for 15 wk. The control group did not train. The primary end point was change in natural killer cell cytotoxic activity in isolated peripheral blood mononuclear cells. Secondary end points were changes in standard hematological variables, whole blood neutrophil function, the phenotypes of isolated mononuclear cells, estimations of unstimulated and phytohemaglutinin-stimulated mononuclear cell function (rate of [3H]thymidine uptake), and the production of proinflammatory [interleukin (IL)-1alpha, tumor necrosis factor-alpha, IL-6] and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-beta1). Statistical tests were two-sided (alpha <0.05). Fifty-two participants completed the trial. Intention-to-treat analyses, which included the baseline value as a covariate, showed significant differences between groups for change in percent specific lysis of a target natural killer cell at all five effector-to-target ratios (adjusted mean between-group change over all 5 effector-to-target ratios = +6.34%; P <0.05 for all comparisons), the lytic activity per cell (adjusted mean between-group change = -2.72 lytic units; P=0.035), and unstimulated [3H]thymidine uptake by peripheral blood lymphocytes (adjusted mean between-group change = +218 per dpm x 10(6) cells; P = 0.007). There were no significant differences between groups for change in any other end point. Exercise training increased natural killer cell cytotoxic activity and unstimulated [3H]thymidine uptake by peripheral blood lymphocytes in postmenopausal breast cancer survivors.     

Therapeutic evaluation of interleukin-1 for stimulation of hematopoiesis in primates after autologous bone marrow transplantation

A multiple dose IL-1 therapy was evaluated for its capability to stimulate hematopoiesis in normal primates and to restore hematopoiesis after autologous bone marrow transplantation. The administration of IL-1 to normal animals over a dose range of 0.5 to 10 ug/kg/d led to a 7-12 fold increase in peripheral blood neutrophil and monocyte counts after 24 hours. This increase in the mature peripheral blood myeloid cells was followed by changes in the myeloid composition of the bone marrow, where the percentage of myeloid elements increased along with a transient increase in myeloid progenitor cell activity. IL-1 treatment also led to an initial decrease in platelet counts of 10-30% during the first 3 days of treatment. However, a striking finding was a significant and long lasting stimulation of increased platelet production with platelet counts increasing to 77% of baseline 3 days after cessation of treatment and remaining elevated for the next 10 days. The therapeutic potential of the IL-1 regimen to restore hematopoiesis was further evaluated in an established autologous bone marrow transplantation model. In monkeys receiving IL-1 doses, 1.0 and 5.0 ug/kg/d, neutrophil counts recovered to >0.5 x 10e9/1 on day 16, one day earlier than control, but the recovery to baseline neutrophil counts occurred 5 days sooner than control. IL-1 therapy had its greatest effect on the restoration of platelet counts after transplantation, reaching >100 x 10e9/l by day 21, two weeks earlier than control. This work demonstrates that IL-1 therapy stimulates myelopoiesis but its most promising clinical application is the stimulation of platelet production.Views presented in this paper are those of the authors: no endorsement by the Department of the Navy or the Defense Nuclear Agency has been given or should be inferred. This work was supported by the Naval Medical Research and Development Command, Research Task No. 63706N MM095.003.1007 and the Defense Nuclear Agency Work Unit No. 132082.     

Innate-immune responses of tilapia (Oreochromis mossambicus) exposure to acute cold stress

In this present study, Oreochromis mossambicus tilapia were transferred to cold water at 12°C for various time intervals (1, 4, 8, 24, and 48 hr) and its innate immune response was analyzed by studying cellular and humoral parameters. In vivo, alternative complement pathway activity in blood plasma was rapidly increased at 1 hr of cold water (12°C) exposure. Lysozyme activity and cortisol levels of plasma were increased at 4 and 1 hr, respectively. Surprisingly, only plasma cortisol levels remained unchanged through 24 hr of cold water transfer. Phagocytic ability, phagocytic capacity, and respiratory burst (RB) activity of head kidney (HK) leukocytes and splenocytes showed no any significant changes. In peripheral blood leukocytes, phagocytic capacity, and RB activity were increased at 24 hr of cold water exposure. The expressions of genes involved innate immunity in splenocytes and HK leukocytes of tilapia cold water exposure were analyzed, messenger RNA (mRNA) expressions of HSP70, HSP90, and immunoglobulin M failed to change upon exposure to cold stress. Major histocompatibility complex-I and II mRNAs were significantly increased in tilapia splenocytes at 1 hr of cold water transferred. Whereas myxovirus (Mx) expression was increased in splenocytes and HK leukocytes of tilapia after 1 hr of cold water exposed. Our result reveals that the exposure of tilapia to acute cold stress condition significantly enhances plasma acid phosphatase activity and both phagocytic capacity and RB activity. Furthermore, cold stress significantly stimulates Mx gene expression in splenocytes and HK leukocytes.