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Biomedical subjects

B K Pedersen

Publications and source records attributed to B K Pedersen.

At least 55 records · Page 3Linked to original sources

Chemokines are elevated in plasma after strenuous exercise in humans.

During the last few years much attention has been paid to the chemokines. Chemokine receptors are necessary to render a target permissive for infection by the human immunodeficiency virus (HIV) and high concentrations of chemokines have been shown to protect against the progression of HIV disease towards death. In the present study, we investigated the capability of strenuous exercise to induce elevated plasma concentrations of the chemokines interleukin (IL)-8, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. Eight male athletes completed the Copenhagen Marathon 1997. Blood was sampled before, immediately after the run and every 30 min during a 4 h recovery period. Plasma chemokine concentrations were measured using enzyme-linked immunosorbent assays. The IL-8, MIP-1 alpha and MIP-1 beta concentrations all peaked 0.5 h after the run when they were 6.7-fold, 3.5-fold and 4.1-fold increased, respectively. The elevated concentrations of chemokines in plasma after exercise could have implications for HIV-infected individuals; a possibility that needs further investigation.

Adult↗

Decreased natural killer cell activity is associated with atherosclerosis in elderly humans.

Well-preserved natural killer cell (NK) activity has been associated with successful aging. The aim of the present study was to perform detailed analyses of NK cell function and to investigate the clinical significance of the NK cell number and function in relationship to health in a large cohort of elderly humans. It was tested if the potential of natural cytotoxicity in the blood (evaluated as an index including cytotoxicity per NK cell and the number of circulating NK cells) was preserved in 174 81-year-old humans versus 91 young controls and if NK cell mediated immunity was associated with age-related inflammatory diseases such as atherosclerosis. Elderly people had decreased cytotoxicity per NK cell in short-term but not in long-term assays. Ca(2+) independent cytotoxicity was unaltered, and NK cells maintained their cytotoxic responses to interleukin-2 and interferon-alpha signals. The decreased cytotoxicity per NK cell was not completely counteracted by increased circulating numbers of NK cells in the blood. Elderly people with severe medical disorders had low numbers of circulating NK cells. Furthermore, elderly people with atherosclerosis had low cytotoxicity per NK cell and a high number of circulating neutrophils.

Adult↗

Hypotension during endotoxemia in aged humans.

BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age 66 yr) received an intravenous bolus injection of Escherichia coli endotoxin (2 ng kg(-1)). Blood pressure, heart rate and core temperature were monitored during the first 7 h. Plasma catecholamine concentrations were measured at hourly intervals. RESULTS: The elderly showed a significantly more pronounced decrease in mean arterial pressure 4-7 h after endotoxin administration compared with the young controls (ANOVA; age x time; P < 0.0005). This mainly reflected a decrease in the systolic blood pressure in the elderly. The heart rate of both groups increased without difference between groups. Increased plasma epinephrine concentrations were found 2-3 h after endotoxin administration in both groups. Five hours after the endotoxin challenge, the epinephrine concentration had returned to control values in the elderly group only, in spite of decreased blood pressure. CONCLUSION: In conclusion, healthy elderly subjects fail to maintain a constant mean arterial pressure in response to the immunological challenge of endotoxemia.

Adult↗

Effects of subcutaneous IL-2 therapy on telomere lengths in PBMC in HIV-infected patients.

In this study we investigated the effect of interleukin-2 (IL-2) on mean terminal restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC). Ten human immunodeficiency virus (HIV)-infected individuals were included and IL-2 was administered subcutaneously with 3 x 106 IU three times a week for 24 weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P = 0.03) and 286 bp at week 8 (P = 0.09). Individual TRF changes at weeks 12, 16, 20 and 24 were highly variable. However, in the 12 weeks following therapy, TRF lengths generally increased reaching baseline levels by the end of the study. At baseline, mean TRF lengths were positively correlated to the ratio of naïve and memory phenotype within both CD4+ and CD8+ cells. This study shows that IL-2 treatment induces transient shortened mean TRF lengths in PBMC from HIV-infected individuals, indicating that IL-2 enhances the lymphocyte count by peripheral proliferation or recruitment of memory T cells into the blood.

Adjuvants, Immunologic↗

N-acetylcysteine attenuates oxidative burst by neutrophils in response to ergometer rowing with no effect on pulmonary gas exchange.

This study evaluated whether the reduction of the neutrophil oxidative burst by N-acetylcysteine improves pulmonary gas exchange during a six minute maximal ergometer row. Healthy trained oarsmen were double-blinded randomized to either N-acetylcysteine (6 g daily for three days) or placebo groups. As determined by the relative changes of the zymosan-stimulated luminol-enhanced chemiluminescence response, N-acetylcysteine suppressed the exercise-induced enhanced neutrophil oxidative burst response to rowing (-7 +/- 6% vs. 17 +/- 8%; P < 0.05). This was the case although the concentration of neutrophils remained similarly elevated above the pre-exercise level in both trials (to 5.4+/-0.5 vs. 5.9+/-0.6 x 10(9) cells x l(-1), respectively, P>0.05). In the placebo and N-acetylcysteine groups, pulmonary ventilation increased and the arterial CO2 partial pressure decreased to the same extent during exercise. Also, at the end of exercise the arterial O2 partial pressure (77 1 vs. 78+/-1 mmHg), haemoglobin O2 saturation (92 +/- 1% vs. 93 +/- 1%) and O2 uptake (5.0 +/- 0.2 vs. 4.9 +/- 0.21 x min(-1)) were not significantly affected by N-acetylcysteine. Equally, two hours after exercise, the pulmonary diffusion capacity was reduced by 7 +/- 2% below the pre-exercise with no significant influence of N-acetylcysteine. We conclude that the neutrophil oxidative burst to exercise does not influence pulmonary gas exchange during and after maximal rowing.

Acetylcysteine↗

Increased neuroendocrine response to a repeated bout of endurance exercise.

This study was designed to compare a first bout of high-intensity endurance exercise with a second bout of similar exercise on the same day, and thereby test the hypothesis that the endocrine response elicited by a second bout is more pronounced compared with a single bout of exercise. Nine male, elite endurance athletes participated in three trials of 24-h duration: 1) complete bed rest (REST), 2) one bout of exercise (ONE), and 3) two bouts of exercise separated by a 3-h rest period (TWO). Each exercise bout consisted of a 10-min warm-up at 50% of VO(2max) followed by 65 min at 75% of VO(2max) on a cycle ergometer. Exercise was performed between 11:00 a.m. and 12:15 a.m. (only in TWO) and 3:15 and 4:30 p.m. (both ONE and TWO). The subjects rested in bed at all hours except when exercising. Blood was sampled 11 times at identical time-points until 7:30 a.m. the next morning. We observed significantly increased levels of epinephrine, norepinephrine, ACTH, cortisol, and growth hormone, and decreased levels of testosterone during and/or after the second bout of exercise compared with the first bout. No difference was observed for insulin, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, free fraction of thyroxin or insulin-like growth factor 1. Thus, this study demonstrates a more pronounced neuroendocrine response to a second bout of exercise on the same day compared with a first/single bout, involving both the sympatho-adrenal system and the hypothalamo-pituitary-adrenal axes.

Adult↗

Aging and proinflammatory cytokines.

Aging is associated with increased inflammatory activity reflected by increased circulating levels of TNF-alpha, IL-6, cytokine antagonists and acute phase proteins in vivo. Epidemiologic studies suggest that chronic low-grade inflammation in aging promotes an atherogenic profile and is related to age-associated disorders (eg, Alzheimer disease, atherosclerosis, type 2 diabetes, etc.) and enhanced mortality risk. Accordingly, a dysregulated production of inflammatory cytokines has an important role in the process of aging. Studies of age-related differences in the production of proinflammatory cytokines in response to acute stimulations in vitro have yielded inconsistent results. However, in vivo infectious models show delayed termination of inflammatory activity and a prolonged fever response in elderly humans, suggesting that the acute phase response is altered in aging. However, a causal relation between the acute phase response and the increased mortality because of bacterial infections in older patients remains to be demonstrated.

Aging↗

Exercise and interleukin-6.

Strenuous exercise induces increased levels in a number of pro-and anti-inflammatory cytokines, natural occurring cytokine inhibitors, and chemokines. Thus, increased plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The concentration of IL-6 increases as much as 100-fold after a marathon race. It has recently been demonstrated that IL-6 is produced locally in contracting skeletal muscles and that the net release from the muscle can account for the exercise-induced increase in arterial concentration. Larger amounts of IL-6 are produced in response to exercise than any other cytokine, IL-6 is produced locally in the skeletal muscle in response to exercise, and IL-6 is known to induce hepatic glucose output and to induce lipolysis. These facts indicate that IL-6 may represent an important link between contracting skeletal muscles and exercise-related metabolic changes.

Cytokines↗

Ageing is associated with a prolonged fever response in human endotoxemia.

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.

Acute-Phase Reaction↗

Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise.

The present double-blinded, placebo-controlled study investigated whether antioxidant vitamin supplementation was able to modulate the cytokine and lymphocyte responses after strenuous eccentric exercise. Furthermore, muscle enzyme release was examined to see whether antioxidant treatment could reduce muscle damage. Twenty male recreational runners randomly received either antioxidants (500 mg of vitamin C and 400 mg of vitamin E) or placebo for 14 days before and 7 days after a 5% downhill 90-min treadmill run at 75% .VO(2 max). Although the supplemented group differed significantly with regard to plasma vitamin concentration before and after exercise when compared with the placebo group, the two groups showed identical exercise-induced changes in cytokine, muscle enzyme, and lymphocyte subpopulations. The plasma level of interleukin (IL)-6 and IL-1 receptor antagonist increased 20- and 3-fold after exercise. The plasma level of creatine kinase was increased sixfold the day after exercise. The concentrations of CD4+ memory T cells, CD8+ memory and naïve T cells, and natural killer cells increased at the end of exercise. The total lymphocyte concentration was below prevalues in the postexercise period. In conclusion, the present study does not support the idea that exercise-induced inflammatory responses are induced by free oxygen radicals.

Adult↗

Plasma interleukin-6 during strenuous exercise: role of epinephrine.

Exercise induces increased levels of plasma interleukin-6 (IL-6) as well as changes in the concentration of lymphocytes and neutrophils. The aim of this study was to investigate a possible role for epinephrine. Seven healthy men participated in an exercise experiment. One month later they received an epinephrine infusion. The exercise consisted of treadmill running at 75% of maximal O(2) consumption for 2.5 h. The infusion trial consisted of 2.5 h of epinephrine infusion calculated to reach the same plasma epinephrine levels seen during the exercise experiment. The plasma concentration of IL-6 increased 29-fold during exercise, with peak levels at the end of exercise. The increase in plasma IL-6 during epinephrine infusion was only sixfold, with the peak value at 1 h after infusion. The lymphocyte concentration increased to the same levels during exercise and epinephrine infusion. The lymphocyte count decreased more in the postexercise period than after epinephrine infusion. The neutrophil concentration was elevated threefold in response to exercise, whereas no change was found in response to epinephrine infusion. In conclusion, the exercise-induced increase in plasma IL-6 could not be mimicked by epinephrine infusion. However, epinephrine induced a small increase in IL-6 and may, therefore, partly influence the plasma levels of IL-6 during exercise. In addition, the results support the idea that epinephrine plays a role in exercise-induced changes in lymphocyte number, whereas epinephrine does not mediate exercise-induced neutrocytosis.

Adult↗

Effect of glutamine supplementation on exercise-induced changes in lymphocyte function.

The purpose of this study was to investigate the possible role of glutamine in exercise-induced impairment of lymphocyte function. Ten male athletes participated in a randomized, placebo-controlled, double-blind crossover study. Each athlete performed bicycle exercise for 2 h at 75% of maximum O(2) consumption on 2 separate days. Glutamine or placebo supplements were given orally during and up to 2 h postexercise. The trial induced postexercise neutrocytosis that lasted at least 2 h. The total lymphocyte count increased by the end of exercise due to increase of both CD3(+)TCR alpha beta(+) and CD3(+)TCR gamma delta(+) T cells as well as CD3(-)CD16(+)CD56(+) natural killer (NK) cells. Concentrations of CD8(+) and CD4(+) T cells lacking CD28 and CD95 on their surface increased more than those of cells expressing these receptors. Within the CD4(+) cells, only CD45RA(-) memory cells, but not CD45RA(+) naive cells, increased in response to exercise. Most lymphocyte subpopulations decreased 2 h after exercise. Glutamine supplementation abolished the postexercise decline in plasma glutamine concentration but had no effect on lymphocyte trafficking, NK and lymphokine-activated killer cell activities, T cell proliferation, catecholamines, growth hormone, insulin, or glucose. Neutrocytosis was less pronounced in the glutamine-supplemented group, but it is unlikely that this finding is of any clinical significance. This study does not support the idea that glutamine plays a mechanistic role in exercise-induced immune changes.

Adult↗

Leukocyte counts and lymphocyte responsiveness associated with repeated bouts of strenuous endurance exercise.

This study compared leukocyte counts and lymphocyte responsiveness during and after a second bout of high-intensity endurance exercise on the same day with the response to a similar but single bout of exercise. Nine athletes participated in three 24-h trials: 1) rest in bed (Rest); 2) one bout of exercise (One); and 3) two bouts of exercise (Two). All bouts consisted of 75 min at approximately 75% of maximal O(2) uptake on a cycle ergometer. Lymphocytes in whole blood were stimulated with monoclonal antibodies against CD2 and assessed by flow cytometry for expression of the early activation molecule CD69. The second bout of exercise in the Two trial was associated with significantly increased concentrations of total leukocytes, neutrophils, lymphocytes, CD4(+), CD8(+), and CD56(+) cells and a significantly decreased percentage of CD56(+) cells expressing CD69 compared with a single bout. Additionally, there was a significantly decreased CD69 fluorescence in CD56(+) cells postexercise. These differences suggest a "carry-over" effect in the immune system from a first to a second bout of exercise on the same day.

Adult↗

Effect of glutamine and protein supplementation on exercise-induced decreases in salivary IgA.

Postexercise immune impairment has been linked to exercise-induced decrease in plasma glutamine concentration. This study examined the possibility of abolishing the exercise-induced decrease in salivary IgA through glutamine supplementation during and after intense exercise. Eleven athletes performed cycle ergometer exercise for 2 h at 75% of maximal oxygen uptake on 3 separate days. Glutamine (a total of 17.5 g), protein (a total of 68.5 g/6.2 g protein-bound glutamine), and placebo supplements were given during and up to 2 h after exercise. Unstimulated, timed saliva samples were obtained before exercise and 20 min, 140 min, 4 h, and 22 h postexercise. The exercise protocol induced a decrease in salivary IgA (IgA concentration, IgA output, and IgA relative to total protein). The plasma concentration of glutamine was decreased by 15% 2 h postexercise in the placebo group, whereas this decline was abolished by both glutamine and protein supplements. None of the supplements, however, was able to abolish the decline in salivary IgA. This study does not support that postexercise decrease in salivary IgA is related to plasma glutamine concentrations.

Adult↗

Strenuous exercise decreases the percentage of type 1 T cells in the circulation.

Prolonged strenuous exercise is followed by a temporary functional immune impairment. Low numbers of CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells are found in the circulation. These cells can be divided according to their cytokine profile into type 1 (Th1 and Tc1), which produce interferon-gamma and interleukin (IL)-2, and type 2 (Th2 and Tc2) cells, which produce IL-4. The question addressed in the present study was whether exercise affected the relative balance between the circulating levels of these cytokine-producing T cells. Nine male runners performed treadmill running for 2.5 h at 75% of maximal oxygen consumption. The intracellular expression of cytokines was detected following stimulation with ionomycin and phorbol 12-myristate 13-acetate in blood obtained before, during, and after exercise. The percentage of type 1 T cells in the circulation was suppressed at the end of exercise and 2 h after exercise, whereas no changes were found in the percentage of type 2 T cells. Plasma epinephrine correlated negatively with the percentage of circulating CD8+ T cells producing IL-2, whereas peak IL-6 correlated with the percentage of CD8+ IL-4-producing T cells in the circulation. Peak plasma IL-6 correlated with plasma cortisol postrunning. In conclusion, the postexercise decrease in T lymphocyte number is accompanied by a more pronounced decrease in type 1 T cells, which may be linked to high plasma epinephrine. Furthermore, IL-6 may stimulate type 2 T cells, thereby maintaining a relatively unaltered percentage of these cells in the circulation compared with total circulating lymphocyte number.

Adult↗

No effect of seasonal variation in training load on immuno-endocrine responses to acute exhaustive exercise.

This study was designed to examine the relationship between seasonal changes in training and competition load, and changes in leukocyte subsets, stress hormones, and interleukin-6 (IL-6) in response to a standardised bout of endurance exercise. In addition, changes in mood states were monitored. Ten male, international Nordic skiers, age 20-29, maximal oxygen uptake 70-82 ml x kg(-1) x min(-1) performed the same incremental treadmill tests to exhaustion at the same time of day (+/-1 h), during the competitive season (in-season HI test) and the recovery season (off-season LO test). The subject filled out a training and competition log (TC score) for three weeks prior to each test and a 65-item Profile of Mood State (POMS) test on arrival at the laboratory. Venous blood for haematological, hormonal, and IL-6 analysis was drawn before and at 0, 15, 30, 60, 120 and 240 min after the test. TC score was more than twice as high during the competitive season (16.0 +/- 3.9) compared to the off-season period (7.0 +/- 4.4). An ANOVA procedure for repeated measures showed no difference in exercise induced changes in concentrations of neutrocytes, lymphocytes, epinephrine, ACTH or cortisol between the in-season HI and off-season LO tests; however, norepinephrine and the IL-6 concentrations were elevated at the in-season HI test compared to the off-season LO test. There were no significant differences in POMS global mood score or sub-scores between the in-season HI and the off-season LO tests. Thus, in a group of elite Nordic skiers, we conclude that a doubling of the training and competition load during the winter season does not alter the leukocyte and stress hormone responses to an incremental exercise test to exhaustion.

Adaptation, Physiological↗

Exercise and cytokines with particular focus on muscle-derived IL-6.

Exercise induces increased circulating levels of a number of cytokines. Thus, increased plasma levels of tumour necrosis factor (TNF)-alpha, interleukin (IL-1) beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The concentration of IL-6 increases up to 100 fold after a marathon race. Recently, it has been demonstrated that IL-6 is produced locally in contracting skeletal muscles and that the net release from the muscle can account for the exercise-induced increase in arterial IL-6 concentration. IL-6 more than any other cytokine is produced in large amounts in response to exercise. It is produced locally in the skeletal muscle in response to exercise, and IL-6 is known to induce hepatic glucose-output and to induce lipolysis. This indicates that IL-6 may represent an important link between contracting skeletal muscles and exercise-related metabolic changes.

Animals↗