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The health benefits of physical activity in children and adolescents: implications for chronic disease prevention.

UNLABELLED: Clinical, epidemiological and basic research evidence clearly supports the inclusion of regular physical activity as a tool for the prevention of chronic disease and the enhancement of overall health. In children, activities of a moderate intensity may enhance overall health, and assist in preventing chronic disease in at-risk youth. The numerous health benefits of regular exercise are dependent on the type, intensity and volume of activity pursued by the individual. These benefits include reduction of low density lipoproteins while increasing high density lipoprotein; improvement of glucose metabolism in patients with type II diabetes; improved strength, self esteem and body image; and reduction in the occurrence of back injuries. In addition, a progressive, moderate-intensity exercise program will not adversely effect the immune system and may have a beneficial effect on the interleukin-2/natural killer cell system. Furthermore, by decreasing sedentary behaviors and, thus, increasing daily physical activity, individuals may experience many stress-reducing benefits, which may enhance the immune system. CONCLUSION: Moderate intensity exercise of a non-structured nature seems to facilitate most of the disease prevention goals and health promoting benefits. With new guidelines promoting a less intense and more time-efficient approach to regular physical activity, it is hoped that an upward trend in the physical activity patterns, and specifically children at risk for chronic disease, will develop in the near future.

Adolescent↗

Specific signaling pathways triggered by IL-2 in human V gamma 9V delta 2 T cells: an amalgamation of NK and alpha beta T cell signaling.

The global immune response can be simplified into two components: the innate and the acquired systems. The innate immune response comprises primarily macrophages and NK cells, while B and T cells orchestrate the acquired response. Human Vgamma9Vdelta2 T cells represent a minor T cell subpopulation in blood (1-5%) that is activated via the TCR by small nonpeptidic molecules. Their percentage dramatically increases during the early phase of infection by intracellular pathogens, and they display many characteristics of NK cells, which places them at a unique position within the immune system. Our aim was to explore the behavior of these cells when they are activated by a receptor that is common to NK and alphabeta T cells, and to determine signaling pathways and biological responses induced in these cells through this receptor. Thus, we investigated whether Vgamma9Vdelta2 T cells behave as NK cells or as alphabeta T cells. We demonstrated that IL-2 activates not only STAT3, STAT5, the phosphatidylinositol 3-kinase pathway, and extracellular signal-regulated kinase-2 pathway, but also STAT4 as in NK cells, and the p38 mitogen-activated protein kinase pathway as in alphabeta T cells. Moreover, IL-2 induces the production of IFN-gamma in Vgamma9Vdelta2 T cells as observed in NK cells. Due to their double profiles, Vgamma9Vdelta2 T cells are at the interface of the innate and the acquired immune response and may therefore not only modulate the activity of innate cells, but also influence Th1/Th2 differentiation.

Cells, Cultured↗

Evolution and integration of innate immune systems from fruit flies to man: lessons and questions.

Despite broad differences in morphology, ecology and behavior, the fruit fly Drosophila melanogaster and humans show a remarkably high degree of conservation for many molecular, cellular, and developmental aspects of their biology. During the last decade, similarities have also been discovered in some of the mechanisms regulating their innate immune system. These parallels regard mainly the Toll-like receptor family and the intracellular signaling pathways involved in the control of the immune response. However, if the overall similarities are important, the detailed pathogen recognition mechanisms differ significantly between fly and humans, highlighting a complicated evolutionary history of the metazoan innate defenses. In this review, we will discuss the main similarities and differences between the two types of organisms. We hope that this current knowledge will be used as a starting point for a more comprehensive view of innate immunity within the broad variety of metazoan phyla.

Animals↗

Asymmetrical distribution of brain interleukin-6 depends on lateralization in mice.

The central nervous system can regulate the peripheral immune system. Moreover, differences between left and right hemispheres (neurochemical brain asymmetries) and behavioral lateralization (functional brain asymmetries) affect immune responses. The molecular basis of brain-immune interactions remains insufficiently understood. Cytokines regulate immune responses, possibly through activation of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis activities are related to behavioral lateralization and brain asymmetry. Given IL-6 plays a role in asymmetrical brain immunomodulation, one might expect the IL-6 distribution in brain to be asymmetrical and to depend on behavioral lateralization. In order to start to test this hypothesis, male C57BL/6J mice were selected for paw preference and assessed for IL-6 levels in right and left cortex and hippocampus by enzyme linked immunosorbent assay. The results showed asymmetrical distribution of brain IL-6 in left-pawed animals and ambidextrous animals, but not in right-pawed animals, both in cortex and hippocampus. Furthermore, we found a correlation between IL-6 hemispheric distribution and the degree of behavioral lateralization both in cortex and hippocampus. Altogether, these results suggest that brain IL-6 could be a mediator of asymmetrical immunomodulation by the central nervous system.

Animals↗

Implications of multiple phenotypes observed in prolactin receptor knockout mice.

The development of a mouse line deficient in the PRL receptor (PRLR) would be an ideal means to better understand the multiple functions of prolactin. We were worried initially that removal of the PRLR from the mouse genome might be lethal and were surprised to find this not to be the case. We identified numerous deficiencies in PRLR knockout (KO) animals. Female homozygous mice are completely infertile and lack normal mammary development, while hemizygotes are unable to lactate following their first pregnancy. PRLR KO males and females have markedly elevated (30- to 100-fold) serum prolactin levels and in some instances pituitary hyperplasia is present. Maternal behavior is severely affected in both hemizygous and heterozygous animals. Bone formation is reduced in young animals and adults (males and females). Recently, we noticed that older KO animals show a slight reduction in body weight which appears to be due to reduced abdominal fat deposition.

Animals↗

Developmental exposure to corticosterone: behavioral changes and differential effects on leukemia inhibitory factor (LIF) and corticotropin-releasing hormone (CRH) gene expression in the mouse.

RATIONALE: Cytokines are found in both the peripheral and central nervous system. There has been increasing interest in their potential role in some of the behavioral features of depressive disorders. Leukemia inhibitory factor (LIF), a proinflammatory cytokine, produces stimulation of adrenocorticotropic hormone (ACTH) secretion in response to emotional and inflammatory stress and recently has been linked to depressive-type behavior. Both the hypothalamic-pituitary-adrenal axis and the immune system, including cytokine-mediated responses, appear to be susceptible to long-term programming during fetal and neonatal development. OBJECTIVE: The present study was designed to characterize the effects of perinatal exposure to corticostereone on behavior, hypothalamic LIF and corticotropin-releasing hormone (CRH) mRNA expression, and basal plasma corticosterone levels in adult female mice. METHODS: Corticosterone was added to the drinking water beginning the last week of gestation and continued until weaning. Behavior in the open field and forced swim tests, baseline plasma corticosterone levels, and hypothalamic LIF and CRH gene expression were evaluated in the adult offspring. RESULTS: Mice exposed to perinatal corticosterone showed increased immobility in the forced swim test and increased locomotor activity in the open field test. Although there were no differences between treatment groups in terms of basal plasma levels of corticosterone or hypothalamic CRH mRNA, LIF mRNA expression was increased in the hypothalamus. CONCLUSIONS: These results show that perinatal exposure to glucocorticoids can produce long-term behavioral changes and upregulation of central LIF mRNA expression.

Animals↗

The brain-immune axis: role of opiates and other substances of abuse, the hypothalamic-pituitary-adrenal axis and behavior.

The brain-immune axis is a highly complex and dynamic homeostatic mechanism. The effect of morphine, or other drugs of abuse, on this interactive system can have multiple consequences, depending on the specific site(s) of action, duration of exposure and underlying neuroendocrine, neural and behavioral status. This emphasizes the critical role of interdisciplinary studies, incorporating behavioral, pharmacological, neuroanatomical, cellular and molecular approaches, that are necessary for elucidating opiate-BIA interactions. To characterize fundamental mechanisms of action, the sheer complexity of this system often requires that more rigorous experimental methodology be applied by multidisciplinary groups of investigators than ever before.

Animals↗

Voluntary consumption of cyclophosphamide by Mrl mice.

Fluid-deprived, lupus-prone Mrl-lpr/lpr and congenic Mrl +/+ mice were provided with a single drinking bottle containing varying concentrations of cyclophosphamide (CY) dissolved in chocolate milk. Eighteen- and 20-week-old Mrl-lpr/lpr males with manifest symptoms of autoimmune disease voluntarily consumed more of the CY solution than Mrl +/+ mice of the same age after 1 week of 1 hr/day exposures. The volume of CY-laced chocolate milk consumed was sufficient to attenuate lymphadenopathy and the elevated anti-DNA antibody titers in these animals. When testing began before the development of manifest symptoms of autoimmune disease, there were no differences between the two substrains. These results are consistent with the hypothesis that behavioral processes can act to correct homeostatic imbalances within the immune system.

Animals↗

Stress and HIV disease progression: psychoneuroimmunological framework.

Psychoneuroimmunology (PNI) is the study of the interrelationships among behavior, neural and endocrine function, and the immune system. PNI investigates the relationships among stress, physiological dysregulation, and health outcomes. Research has supported the theory that emotional distress and the resultant neuroendocrine activation can induce immune system suppression. This suppression has significant implications for disease susceptibility and progression. HIV disease and its extensive immunological consequences are explored within this framework. Potential physiological pathways that may mediate stress-induced dysregulation within the context of HIV disease are identified. Key HIV-related PNI research studies are reviewed and critically analyzed. Implications for nursing practice and research are discussed.

Disease Progression↗

Acute and chronic airway responses to viral infection: implications for asthma and chronic obstructive pulmonary disease.

Despite the high clinical impact of established and emerging respiratory viruses, some critical aspects of the host response to these pathogens still need to be defined. In that context, we aimed at two major issues: first, what are the innate immune mechanisms that control common respiratory viral infections; and second, whether these mechanisms also cause long-term airway disease. Using a mouse model of viral bronchiolitis, we found that antiviral defense depends at least in part on a network of mucosal epithelial cells and macrophages specially programmed for immune-response gene expression. When this network is compromised, the host is highly susceptible to infection, but network components can be engineered to provide increased resistance to infection. Similar alterations appear in asthma and chronic bronchitis/chronic obstructive pulmonary disease, suggesting that evolving attempts to improve antiviral defense may also lead to inflammatory airway disease. Indeed, in genetically susceptible mice, respiratory paramyxoviruses cause a "hit and run" phenomenon that is manifested by the development of a permanent airway disease phenotype long after the infection has cleared. The phenotype can be segregated into individual traits to achieve more precise definition of just how viruses reprogram host behavior. Identifying specific components of the mucosal immune system that manifest an aberrant antiviral response may thereby allow for adjusting this response to improve acute and chronic outcomes after viral infection.

Animals↗

Behavioral correlates of sympathoadrenal reactivity: the toughness model.

Research with humans is reviewed showing that increased levels of urinary epinephrine (EPI) and norepinephrine (NE) from samples taken following mental challenge/stress situations are associated with better performance in those situations and with emotional stability. Another research tradition with humans and animals shows that various training protocols lead to increased peripheral and central catecholamine capacities. Those training protocols include continuous exposure to cold, periodic exposure to some intermittent stressors such as foot or tail shock (with intervening rest periods), or programs of aerobic exercise. While increasing catecholamine capacities, those procedures also result in lower base rates of the catecholamines and with the delay of pituitary-adrenal-cortical responses in challenge/stress contexts. That physiological pattern of "toughness" leads to improved performance in challenge/stress situations, increased tolerance of stressors (i.e., reduced behavioral suppression or depression), emotional stability, and immune system enhancement. The special conditions are discussed that are required for demonstrating increased catecholamine capacities rather than the attenuation of arousal associated with increased muscular and neuroendocrine efficiency. Finally, the role played by toughness in reducing anxiety while increasing energy in challenge/stress situations is discussed.

Adaptation, Psychological↗

A cellular automata model of tumor-immune system interactions.

We present a hybrid cellular automata-partial differential equation model of moderate complexity to describe the interactions between a growing tumor next to a nutrient source and the immune system of the host organism. The model allows both temporal and two-dimensional spatial evolution of the system under investigation and is comprised of biological cell metabolism rules derived from both the experimental and mathematical modeling literature. We present numerical simulations that display behaviors which are qualitatively similar to those exhibited in tumor-immune system interaction experiments. These include spherical tumor growth, stable and unstable oscillatory tumor growth, satellitosis and tumor infiltration by immune cells. Finally, the relationship between these different growth regimes and key system parameters is discussed.

Cell Cycle↗

Beneficial influences of systemic cooperation and sociological behavior on longevity.

During his long research career in the field of aging, Dr Bernard Strehler developed a series of theories concerning the identity of genes that can promote longevity and their role in natural selection. As a tribute to Dr Strehler, we have taken this opportunity to summarize a selection of these theories and to illustrate how these insights have influenced our search for longevity genes within the immune system. The identification of longevity genes has proven difficult. We believe that, at least in part, this reflects the emphasis on the concept of survival of the 'physically' fittest. We have used the immune system as a model to demonstrate that, over and above the self-evident advantage of those genes that contribute the attributes commonly associated with survival of the 'physically' fittest, those genes that lead to a predisposition to cooperate also confer a competitive survival advantage. As the acquisition of cooperativity in a society is linked to support mechanisms provided by older individuals, the search for longevity genes should not be limited to those genes that are associated with extended expression of a youthful phenotype. Rather these studies should be expanded to include identification of those genes that regulate physiologic parameters that affect individual longevity, even if they do not correspond with the traditional view of reproductive competitiveness. At the societal level, longevity genes may encode attributes that regulate sociologic or psychological parameters that may contribute to a tendency to non-aggressive or cooperative behavior that leads to achievement of common goals necessary for the survival of the species. This view of the selection for longevity impacts the analysis of longevity genes and aging at the organismal level. Dr Strehler viewed organismal aging as an integrated functional state, in which he conceived the outcome as reflecting the net balance of functional decrementers and evolved compensatory features. We propose that, in more evolved species, the longevity genes will be those genes, or sets of genes, that counterbalance of age-related functional decrementers with the age-related manifestation of evolved compensatory features. Thus, as illustrated here through analysis of the immune system, the longevity genes may well be those genes that promote overall systemic cooperation and compensation within the immune system and associated systems, rather than the genes that prevent age-related alterations in only one or a limited number of pathways.

Aging↗

Effects of social status after mixing on immune, metabolic, and endocrine responses in pigs.

The effects of social rank on immune, metabolic, and endocrine responses were studied in 10 newly mixed groups of German Landrace pigs (9 individuals each) at an age of 12 weeks. Immediately after mixing, the agonistic interactions (AI) of all group members were continuously recorded over 3 days (10 h daily). An individual dominance value (DV) was calculated by the number of wins minus defeats in relation to all decisive fights (DV < or = 0, subordinate; DV > 0, dominant). Blood samples were taken 24 h before and 3 days after mixing. The data showed that the social status had a significant effect on lymphocyte proliferation in responses to different mitogens: socially dominant pigs had higher proliferative response than subordinate pigs. In addition, during the observation period the lymphocyte activation by mitogens increased in the dominant animals and decreased in the subordinate animals with increasing number of agonistic interactions. The rise in total serum IgG concentration 3 days after mixing was higher in dominant pigs compared with subordinates. The dominance status did not significantly affect plasma metabolic levels nor cortisol concentrations. However, mixing appeared to increase glucose and total protein values and to decrease alkaline phosphatase and cortisol levels in both, dominant and subordinate pigs. In conclusion, mitogen induced cell proliferation seems to be a valuable marker for acute social stress in pigs.

Agonistic Behavior↗

Design and implementation of an immune system simulator.

Cellular automata based models have proven capable of providing several new insights into the dynamics of the immune system (IS) response.A qualitative picture of the IS behavior can be obtained with small-scale simulations. However, for a more detailed analysis and to further validate the models, large-scale simulations are required. To this purpose we present here a simulator (PARIMM) of the IS response which has been carefully designed and coded to allow such simulations (millions of cells with a very high degree of complexity). The code does not just resort to parallel processing to run faster. Data structures and I/O have been optimized as well to limit the (huge) memory and disk space requirements. The recent addition of the description of the T killer cellular mediated response allows the code to simulate both humoral and cellular immune reactions. All these features put PARIMM among the most complete simulators of the immune system developed up today.

Animals↗

[Psychoneuroimmunology. A new approach to the function of immunological system].

The most recent evidence suggests that the immune system responses are not regulated only by the presence of antigens but they are also influenced by the brain and behavior. It has been known for some time that stressful conditions alter the functioning of the immune system. Despite methodological difficulties in the quantitation of stress, and its association with the onset of illness, the concept of the stress impact on susceptibility to several diseases is widely acknowledged. This paper reviews the effects of stress on the endocrine and central nervous systems and presents the interactions between these systems and the immune response after exposure to stress signals.

Antigens↗

[Effect of stress and immune stimulus on the pituitary-adrenal axis in gray rats selected for behavior].

A comparison of effects of the restrain stress, and lipopolysaccharide and interleukin-2 treatment on pituitary-adrenal system of tame and aggressive rats, was examined. It was found that plasma ACTH and corticosterone levels in response to restrain stress and lipopolysaccharide treatment were significantly decreased in the tame rats compared to aggressive ones. By contrast, the maximum corticosterone level was the same in plasma of both groups after interleukin-2 treatment, although the time patterns of the response were different. Thus the selection of wild grey rats for tame behavior results in change of the response of the pituitary-adrenal axis to the immune stimulus. It is conceivable that the interaction between pituitary-adrenal axis and immune system also changes in tame rats.

Adrenocorticotropic Hormone↗