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Biomedical subjects

H Bruunsgaard

Publications and source records attributed to H Bruunsgaard.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cytokines in aging and exercise.

Aging is associated with increased inflammatory activity. Increased plasma levels of tumour necrosis factor (TNF)-alpha were found in centenarians aged 100 years and in individuals aged 80-81 years when compared to a young control group. Plasma levels of TNF-alpha were linearly correlated to plasma levels of interleukin (IL)-6, TNF-receptors and C-reactive protein. High levels of TNF-alpha were directly related to dementia and to a low blood pressure ankle-arm index, indicating generalized atherosclerosis. In hospitalized patients with Streptococcus pneumonia infection, aging was associated with prolonged inflammatory activity. Similar results were found using an in vivo endotoxin challenge model in old versus young humans. Strenuous exercise induces increased levels in a number of proinflammatory and anti-inflammatory cytokines, naturally occurring cytokine inhibitors and chemokines. Thus, increased plasma levels of TNF-alpha, IL-1, IL-6, IL-1 receptor antagonist (IL-Ira), TNF-receptors (TNF-R), IL-10, IL-8 and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The cytokine response to strenuous exercise has similarities to the cytokine response to trauma and sepsis. Therefore, in future studies, exercise is suggested as an ethically applicable model to use in studies on mechanisms underlying the age-associated altered cytokine response.

Adult↗
PubMed2000

Special feature for the Olympics: effects of exercise on the immune system: effects of exercise on the immune system in the elderly population.

Immunosenescence is characterized by impaired cellular immune function concomitant with increased inflammatory activity. Immune dysfunction is associated with increased mortality risk in elderly people. An important part of human ageing is characterized by a decline in the ability of individuals to adapt to environmental stress. Exercise has been suggested as a prototype for studying the effects of stress factors on the cellular immune system. Studies of interactions between an acute bout of exercise and immune function may be a useful and an ethically acceptable tool to investigate cell trafficking, immune mobilization/deficiency and the acute phase response during physical stress situations in relation to human ageing. Elderly humans have a preserved ability to recruit T lymphocytes and NK cells in response to an acute bout of exercise. Physical exercise training programs do not result in major restoration of the senescent immune system in humans. However, highly conditioned elderly humans seem to have a relatively better preserved immune system, although it is not possible to conclude if this is linked to training or other lifestyle-related factors.

Adolescent↗
PubMed1999

Exercise induces recruitment of lymphocytes with an activated phenotype and short telomeres in young and elderly humans.

This study was performed in order to investigate the type of T cells recruited to the blood in response to an acute bout of exercise with regard to mean lengths of telomeric terminal restriction fragments (TRF) and surface activation markers and with special emphasis on age-associated differences. Ten elderly and ten young humans performed maximal bicycle exercise. There was no difference in the number of recruited CD4+ and CD8+ cells between the young and elderly group. In both age groups the immediate increases could be ascribed to recruitment of CD28- cells (CD8+ and CD4+ cells) and memory cells (only CD8+ cells). Furthermore, after exercise mean TRF lengths were significantly reduced in blood mononuclear cells and in CD8+ cells from young subjects and in CD4+ cells from elderly subjects compared with lengths pre-exercise. These findings suggest that the mobilization of T lymphocytes during acute exercise is mainly a redistribution of previously activated cells with an increased replicative story than cells isolated from the blood at rest. Furthermore, elderly humans fulfilling the Senieur protocol have a preserved ability to recruit T lymphocytes in response to acute physical stress.

Adult↗
PubMed1999

Exercise and the immune system--influence of nutrition and ageing.

In essence, the immune system is enhanced during moderate and severe exercise, and only intense long-duration exercise is followed by impairment of the immune system. The latter includes suppressed concentration of lymphocytes, suppressed natural killer cell activity, lymphocyte proliferation and secretory IgA in saliva. During the time of immune impairment, referred to as "the open window", microbial agents, especially viruses may invade the host and infections may be established. One reason for the "overtraining effect" seen in elite athletes could be that this window of opportunism for pathogens is longer and the degree of immunosuppression more pronounced. Alterations in metabolism and metabolic factors may contribute to exercise-associated changes in immune function. Reductions in plasma-glutamine concentrations, altered plasma-glucose level, free oxygen radicals and prostaglandins (PG) released by the elevated number of neutrophils and monocytes may influence the function of lymphocytes and contribute to the impaired function of the later cells. Thus, nutritional supplementation with glutamine, carbohydrate, anti-oxidants or PG-inhibitors may, in principle, influence exercise-associated immune function. Although several intervention studies have been performed, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.

Aging↗
PubMed1999

Exercise and immune function: effect of ageing and nutrition.

Strenuous exercise is followed by lymphopenia, neutrophilia, impaired natural immunity, decreased lymphocyte proliferative responses to mitogens, a low level of secretory immunoglobulin A in saliva, but high circulating levels of pro- and anti-inflammatory cytokines. These exercise-induced immune changes may provide the physiological basis of altered resistance to infections. The mechanisms underlying exercise-induced immune changes are multifactorial and include neuroendocrinological and metabolic mechanisms. Nutritional supplementation with glutamine abolishes the exercise-induced decline in plasma glutamine, but does not influence post-exercise immune impairment. However, carbohydrate loading diminishes most exercise effects of cytokines, lymphocyte and neutrophils. The diminished neutrophilia and elastase (EC 3.4.21.37) responses to eccentric exercise in elderly subjects were enhanced to levels comparable with those of young subjects by fish oil or vitamin E supplements. However, although vitamin C supplementation may diminish the risk of contracting an infection after strenuous exercise, it is not obvious that this effect is linked to an effect of vitamin C on exercise-induced immune changes. In conclusion, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.

Aging↗
PubMed1999

Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans.

Ageing is associated with decreased resistance to bacterial infections and concomitant increased circulating levels of inflammatory cytokines. The purpose of the present study was to research age-related changes in levels of early mediators of the acute-phase response in whole blood supernatants following LPS stimulation, representing an ex vivo model of sepsis. Levels of tumour necrosis factor-alpha (TNF-alpha), IL-1beta and IL-6 in whole blood supernatants were measured after in vitro LPS stimulation for 24 h in 168 elderly humans aged 81 years from the 1914 cohort in Glostrup, Denmark and in 91 young controls aged 19-31 years. Levels of TNF-alpha and IL-1beta were significantly lower in elderly humans compared with young controls, whereas no difference was detected with regard to IL-6. Elderly humans with low body mass index had the lowest levels of IL-1beta. Young women had lower levels of proinflammatory cytokines compared with young men, but this difference was blurred by ageing. No relation was found between circulating plasma levels of TNF-alpha and levels after in vitro LPS stimulation. In conclusion, decreased production of TNF-alpha and IL-1beta after exposure to LPS may reflect impaired host defence against infections in the elderly and be of importance in elderly humans with underlying health disorders. However, the clinical relevance is questionable in healthy elderly people because decreased levels were found compared with young men but not compared with young women.

Adolescent↗
PubMed1999

Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections.

Levels of circulating cytokines were measured in 22 hospitalized patients with pneumococcal infections during the first week after admission, to test for age-associated differences. Twenty-two healthy age- and sex-matched subjects were included as controls. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-1 receptor antagonist, soluble TNF receptor I (sTNFR-I), and IL-10 were increased on admission (P<.05), but macrophage inflammatory protein (MIP)-1beta was not. Whereas levels of cytokines were similar on admission, levels of TNF-alpha and sTNFR-I after 1 week were higher (P<.05) in elderly (68-91 years) than in young (37-55 years) patients. Furthermore, plasma levels of IL-10 and sTNFR-I after 1 week were positively correlated with age, and the declines in sTNFR-I and in the TNFalpha/IL-10 ratio from day 0 to day 7 were correlated with age. Thus, aging was associated with prolonged inflammatory activity. This may reflect decreased ability to control the infection or a dysregulated cytokine response.

Adult↗
PubMed1999

A high plasma concentration of TNF-alpha is associated with dementia in centenarians.

BACKGROUND: Inflammatory mechanisms and immune activation have been hypothesized to play a role in the pathogenesis of age-associated diseases such as dementia and atherosclerosis. The purpose of this study was to evaluate the plasma concentration of tumor necrosis factor (TNF)-alpha in a large cohort of centenarians and to look for its possible associations with cognitive function, atherosclerosis, and general health status. Furthermore, we investigated whether the concentration of TNF-alpha was correlated with the blood concentration of leucocyte subsets or the plasma concentrations of interleukin (IL)-6, soluble TNF receptor 11 (sTNFR-H) (75 kDa) and C-reactive protein (CRP). METHODS: Plasma TNF-alpha was measured by ELISA in 126 centenarians, 45 subjects aged 81 years, 23 subjects aged 55-65 years, and 38 subjects aged 18-30 years. Atherosclerosis was evaluated by the ankle-brachial blood pressure index, and general health status was evaluated by the body mass index and the number of diagnoses present. RESULTS: The concentration of TNF-alpha was significantly increased in 126 centenarians compared to younger control groups, and a high concentration of TNF-alpha was associated with both Alzheimer's disease and generalized atherosclerosis in the centenarians. The concentration of TNF-alpha was positively correlated with the concentrations of plasma IL-6, sTNFR-II, and CRP. No associations were found with increased leucocyte subsets or the body mass index. CONCLUSION: This study demonstrates that, even in apparently healthy subjects, age-associated immune activation indicated by raised levels of pro-inflammatory cytokines may reflect age-associated pathological processes that develop over decades.

Adolescent↗
PubMed1998

The cytokine response to strenuous exercise.

Strenuous exercise is accompanied by an increase in circulating proinflammatory and inflammation responsive cytokines, having some similarities with the response to sepsis and trauma. The sequential release of tumour necrosis factor-alpha, interleukin (IL) 1 beta, IL-6, and IL-1 receptor antagonist (IL-1ra) in the blood is comparable to that observed in relation to bacterial diseases. Eccentric exercise is associated with an increase in serum IL-6 concentrations and is significantly correlated with the concentration of creatine kinase (CK) in the following days, whereas no changes are found after the concentric exercise; this demonstrates a close association between exercise-induced muscle damage and increased serum levels of IL-6. The time course of cytokine production, the close association with muscle damage, and the finding of mRNA-IL-6 in skeletal muscle biopsies after intense exercise all support the idea that during eccentric exercise myofibers are mechanically damaged and that this process stimulates the local production of inflammatory cytokines. It remains to be shown whether systemic endotoxemia during exercise is also a cause of elevated levels of cytokines in the plasma. The present review also discusses the possible roles of protein breakdown, delayed onset muscle soreness, and clinical implications of the acute-phase response following exercise.

Cytokines↗
PubMed1998

Implications of hormesis for biomedical aging research.

Rather than being an exception, non-linearity between dose and response are the rule in biological systems. It might even be anticipated that at some doses a response opposite to that seen at high doses could be elicited (hormesis). Such non-linearity with dose has multiple implications for numerous aspects of biomedical research on aging and for experimental design. Moreover, the implications of such non-linearity are such that governmental regulatory activities and other areas of public health administration will be affected to a large extent once hormesis is widely recognized. The implications with regard to environmental intervention and subsequent regulatory decisions will certainly profoundly affect the political process, as well.

Aged↗
PubMed1997

Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage.

1. This study was performed to test the hypothesis that the exercise-induced increase in circulating cytokine levels is associated with muscle damage. Nine healthy young male subjects performed two high-intensity bicycle exercise trials separated by two weeks. The first trial consisted of 30 min of normal bicycle exercise (concentric exercise), whereas the second consisted of 30 min of braking with reversed revolution (eccentric exercise). The work loads were chosen to give the same increases in heart rate and catecholamine levels in the blood during each trial. 2. Significant increases (P < 0.05) in plasma concentration of creatine kinase (CK), aspartate aminotransferase and alanine aminotransferase were observed only after the eccentric exercise. Furthermore, the level of interleukin-6 (IL-6) in serum increased significantly after the eccentric exercise and was significantly correlated to CK concentration in the following days, whereas no significant changes were found after the concentric exercise. 3. The total concentration of lymphocytes increased significantly (P < 0.05) as a result of eccentric compared with concentric exercise. This was mainly due to a significantly more pronounced recruitment of natural killer (NK) cells and CD8 positive cells (CD8+ cells) during the eccentric trial. However, no significant differences between the two types of work were found in regard to the circulating concentration of monocytes. The concentration of neutrophils was only significantly increased 2 h after the concentric exercise. 4. The finding that high-intensity eccentric exercise caused a more pronounced increase in the plasma level of IL-6, compared with concentric exercise, supports the hypothesis that the post-exercise cytokine production is related to skeletal muscle damage. The fact that no differences between eccentric and concentric exercise were found in the recruitment of most blood mononuclear cell subsets to the blood supports the hypothesis that the exercise-induced increase in plasma catecholamines is a major determinant of the mobilization of these cells into the blood. However, as eccentric exercise caused a more pronounced increase in the concentration of NK cells and CD8+ cells, factors involved in muscle damage may also contribute to the recruitment of these cells.

Adult↗
PubMed1997

Clinical progression of HIV infection: role of NK cells.

The purpose of the study was to examine how immune parameters related to non-major histocompatibility complex (MHC) restricted cytotoxicity changed with respect to progression and duration of human immunodeficiency virus (HIV) infection. Forty-one HIV seropositive subjects with a known time for seroconversion were included. The major finding was that a low percentage and number of natural killer (NK) cells were found in the group who had a rapid progression to acquired immune deficiency syndrome (AIDS) (less than 70 months following seroconversion) compared with those progressing more slowly to AIDS (more than 70 months following seroconversion). Furthermore, a significant correlation was found between the number of months from seroconversion to the diagnosis of AIDS and percentages of CD16+ cells (rs = 0.811, P < 0.01), CD56+ cells (rs = 0.647, P < 0.05), and CD16+CD56+ cells (rs = 0.839, P < 0.01) as well as the concentration of CD16+CD56+ cells in the blood (rs = 0.699, P < 0.05) No differences were found in percentages and concentrations of NK cell subsets between subjects with a long history (more than 6 years) versus a short history (less than 6 years) of HIV infection without AIDS. Furthermore, no negative correlations were found between the concentration of any NK subsets and the number of months since seroconversion in HIV seropositive individuals without AIDS. The total concentration of CD16+, CD56+, and CD16+CD56+ cells was lower in the group of HIV seropositive subjects compared with HIV seronegative subjects (age and sex matched), and the concentration of CD16+ cells was lower in those with AIDS than in those without AIDS. In conclusion, low concentration of NK cells in the blood was associated with a more rapid disease progression, indicating that defective non-MHC restricted cytotoxicity may be associated with HIV disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Exercise-induced immunomodulation--possible roles of neuroendocrine and metabolic factors.

Acute muscular exercise induces an increased neutrophil count concomitant with recruitment of natural killer (NK), B and T cells to the blood as reflected by an elevation in the total lymphocyte count. Meanwhile, following intense exercise of long duration the lymphocyte count declines, non-MHC-restricted cytotoxicity is suppressed, but the neutrophil concentration increases. In relation to eccentric exercise involving muscle damage, the plasma concentrations of interleukin-1, interleukin-6 and the tumor necrosis factor are elevated. In this review we will propose a model based on the possible roles that stress hormones play a mediating the exercise- related immunological changes: adrenaline and to a lesser degree noradrenaline are responsible for the immediate effects of exercise on lymphocyte subpopulations and cytotoxic activities. The increase in catecholamines and growth hormone mediate the acute effects of exercise on neutrophils, whereas cortisol may be responsible for maintaining lymphopenia and neutrocytosis after exercise of long duration. Lastly, the role of beta-endorphin is less clear, but the cytokine response is closely related to muscle damage and stress hormones do not seem to be directly involved in the elevated cytokine level. Other possible mechanisms of exercise-induced immunomodulation may include the so-called glutamine hypothesis, which is based on the fact that skeletal muscle is an important source of glutamine production and that lymphocytes are dependent on glutamine for optimal growth. Furthermore, physiological changes during exercise, e.g. increased body temperature and decreased oxygen saturation may also in theory contribute to the exercise-induced immunological changes.

Catecholamines↗
PubMed1997

In vivo cell-mediated immunity and vaccination response following prolonged, intense exercise.

Epidemiological and experimental studies have shown increased frequency and severity of infections after intense, long-term exercise. This study examines whether an in vivo impairment of the cell-mediated immunity and antibody production can be demonstrated after intense, long-term exercise. Twenty-two male triathletes performed one-half an ironman (group A). Vaccinations with tetanus and diphtheritis toxoid and purified pneumococcal polysaccharide were given after the exercise. Furthermore, a skin test with seven different antigens was applied on the forearm. Antibody titers were measured before and 2 wk after the exercise. The skin test was read 48 h after the application. Eleven non-exercising triathletes (group B) and 22 moderately trained men (group C) were used as control groups. Group A revealed a significantly lower skin test response to the tetanus antigen than both groups B and C. In group A, a smaller cumulative response (sum of the diameters of indurations and number of positive skin test spots) was found than in both groups B and C. No differences in antibody titers were found among the three groups. Thus, the in vivo cell-mediated immunity was impaired in the first days after prolonged, high intensity exercise, whereas there was no impairment of the in vivo antibody production measured 2 wk after vaccination.

Adult↗
PubMed1995

Increase in percentage of CD45RO+/CD8+ cells is associated with previous severe primary HIV infection.

The purpose of the study was to examine how memory (CD45RO) and naive (CD45RA) phenotypes of CD4+ and CD8+ T-cell subpopulations changed with respect to progression and duration of human immunodeficiency virus (HIV) infection. Forty-three HIV-seropositive (HIV+) subjects with known time for seroconversion were included in this cross-sectional study. They were divided into the following groups for comparison: persons with and without AIDS, persons who had seroconverted > 72 and < 72 months before entering the study, persons with or without previous severe primary infection, persons who had developed AIDS > 72 and <72 months before entering the study. Furthermore, the HIV+ group was compared with an HIV-seronegative (HIV-) age- and sex-matched group. There was no difference in the proportion of total naive relative to total memory cells between HIV+ and HIV- subjects, showing an equal loss of naive and memory CD4+ cells in this study. Moreover, there was no difference in the proportion of total naive relative to memory CD8+ cells, showing an equal increase in both subgroups of CD8+ cells in HIV+ subjects. However, HIV+ subjects who had experienced severe primary symptoms resembled the AIDS group regarding shift in the CD8 phenotype from naive to memory and by down-regulation of amounts of CD45RA protein. Furthermore, the results showed that during infection with HIV the amounts of both CD45RA and CD45RO markers on CD4+ cells and CD45RA on CD8+ cells were down-regulated, although with different kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗