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Biomedical subjects

J Halkjaer-Kristensen

Publications and source records attributed to J Halkjaer-Kristensen.

At least 19 recordsLinked to original sources

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

Growth hormone deficiency and hyperthermia during exercise: a controlled study of sixteen GH-deficient patients.

Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH-deficiency may be at risk for developing hyperthermia. To pursue this, we performed a controlled study on sweating and body temperature regulation during exercise in the heat in 16 GH-treated GH-deficient patients with normalized insulin-like growth factor-I and insulin-like growth factor/binding protein-3 serum levels [11 with multiple pituitary deficiency (MPD) and 5 with isolated GH deficiency] and in 10 healthy subjects as controls (CTs). Each subject exercised on a bicycle ergometer for 60 min at a workload corresponding to 45% of their individual maximal oxygen consumption (VO2max), in a room maintained at 35 C. GH serum concentrations increased significantly after approximately 10 min of exercise in the CTs (P < 0.001) but remained low in the patients. Body heat storage was significantly higher in the patients compared with the CTs [89 (SE +/- 10) watts (MPD) vs. 37 (SE +/- 8) watts (CTs), P < 0.001]. Consequently, the core temperatures of the patients increased significantly after exercise compared with those of the CTs [38.3 C (0.10 C) (MPD) and 38.1 C (0.06 C) (isolated GH deficiency) vs. 37.5 C (0.2 C) (CTs) (P < 0.004)]. Skin temperature increased significantly during exercise in the patients but remained unaltered in the CTs. Sweat secretion rates, as determined by the pilocarpine method, were significantly lower in the MPD patients [77 (SE +/- 10) mg/30 min] than in the CTs [115 (SE +/- 7) mg/30 min] (P < 0.005). Total body sweating was lower in the patients than in the CTs, although the difference did not reach statistical significance. Significantly reduced estimated evaporative heat loss was demonstrated in the patients compared with the CTs (P < 0.001). In conclusion, 1) decreased sweating, decreased sensitivity of the sweat gland, and impaired thermoregulation are part of the adult GH-deficiency syndrome, and 2) GH-deficient patients are at risk for developing hyperthermia during physical activity in hot environments.

Adolescent

Evidence that the effect of bicycle exercise on blood mononuclear cell proliferative responses and subsets is mediated by epinephrine.

The present study was designed to test the hypothesis that the exercise-induced changes in blood mononuclear cell (BMNC) subsets, BMNC proliferative responses and lymphokine activated killer (LAK) cell activity are mediated by increased epinephrine concentrations. Healthy male volunteers 1) exercised on a bicycle ergometer (75% of VO2max, 1 h) and 2) on another day were given epinephrine as an intravenous infusion to obtain plasma epinephrine concentrations comparable with those seen during exercise. Blood samples were collected in the basal state, during the last minutes of exercise or epinephrine infusion and 2 h later. During both perturbations the %CD3+ and %CD4+ T cells declined and the %CD16+ NK cells increased. Two h afterwards the CD14+ monocytes increased, while no changes were observed in %CD8+ T cells or %CD20+ B cells. The phytohemagglutinin (PHA) response declined during both epinephrine infusion and exercise experiments. The changes in interleukin-2 (IL-2) effect on proliferation and cytotoxic activity (LAK cell activity) were more pronounced in exercise experiments than during epinephrine. Exercise and epinephrine caused increase in concentrations of lymphocytes and neutrophils, but the changes were more pronounced in exercise experiments. The results indicate that, in response to physical exercise, the rise in plasma epinephrine may contribute to the changes in cellular immunity.

Adult

Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC.

The present study investigated the effect of concentric exercise on cytokine plasma levels and cytokine pre-mRNA in blood mononuclear cells (BMNCs). Healthy young moderately trained men performed ergometer bicycle exercise for 1 h at 75% of maximal oxygen uptake. The levels of plasma interleukin (IL)-6 increased significantly during exercise, but plasma levels of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were below the detection limit in most subjects. Pre-mRNA for IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha could be detected in BMNCs, but the amounts did not change in relation to exercise. These results indicate that, although the absolute number of monocytes increases during exercise and the percentage of CD14+/HLA-DR+ and CD14+/HLA-DR- monocytes increases after exercise, the increased plasma levels of IL-6 during exercise is not likely to be a result of activated monocytes in peripheral blood.

Adult

The effect of acute exercise on lymphocyte subsets, natural killer cells, proliferative responses, and cytokines in HIV-seropositive persons.

Eight healthy men infected with human immunodeficiency virus, type 1 (HIV) and eight HIV seronegative age- and sex-matched controls exercised on a bicycle ergometer (75% of VO2max, 1 h). The percentages of CD4+, CD4+45RA+, and CD4+45RO+ cells did not change, whereas the absolute number of CD4+ cells increased twofold during exercise and fell below prevalues 2 h after. The neutrophil count increase was more pronounced after exercise in the controls compared with in HIV-seropositive subjects. The percent CD16+ cells, and the natural killer (NK) and lymphokine activated killer (LAK) cell activity increased during exercise, but this increase was significantly less pronounced in the HIV-seropositive group. The results suggest that in response to physical stress, HIV-seropositive subjects have an impaired ability to mobilize neutrophils, NK and LAK cells to the blood. Furthermore, because the total number of CD4+ cells, but not the percentage of CD4+ cells, changed in response to exercise, this study further strengthens the idea that the percentage of CD4+ cells is preferable to the number of CD4+ cells in monitoring patients seropositive for HIV.

Adult

The effect of light, moderate and severe bicycle exercise on lymphocyte subsets, natural and lymphokine activated killer cells, lymphocyte proliferative response and interleukin 2 production.

The purpose of the present study was to evaluate the effect of acute bicycle exercise at different exercise intensities on the immune system. Six healthy volunteers exercised on a bicycle ergometer for 1 h at 25%, 50% and 75% of VO2max with an interval of 2 to 3 weeks. Blood samples were collected in the basal state, at the end of exercise and 2 h later. The absolute concentrations of all lymphocyte subsets increased during and fell after exercise at 50% and 75% of VO2max, but did not change significantly at 25% of VO2max. However, at all exercise levels, the percentage of CD3+ blood mononuclear cells decreased due to a decline in the fraction of CD4+ cells. This decline was most pronounced at 75% of VO2max. The fraction of NK cells expressing either the CD16 or the CD56 marker increased during exercise and declined to prevalues 2 h later, however the changes were most pronounced at 75% of VO2max. The natural killer (NK) cell and lymphokine activated killer (LAK) cell activities (lysis per fixed number of mononuclear cells) were increased during all exercise intensities, but were only suppressed below basal levels after exercise at 75% of VO2max. Indomethacin in vitro abolished the post-exercise suppression of NK cell activity and the proportion of CD14+ monocytes increased 2 h after exercise only at 75% of VO2max. These findings indicate that after exercise NK cell function is inhibited by prostaglandins released by monocytes. During exercise at 50% and 75% of VO2max the proliferative response of blood mononuclear cells (BMNC) following stimulation with phytohaemagglutinin A (PHA) decreased, whereas that following stimulation with interleukin-2 (IL-2) was enhanced. The IL-2 production by BMNC in vitro was markedly decreased during and after exercise at 75% of VO2max and this inhibition could be abolished by indomethacin in vitro. In conclusion, the response of the immune system to exercise depends on exercise intensity. In essence, the response is enhanced during exercise, however, after heavy exercise it is suppressed due to an increased level of prostaglandins produced by the elevated number of monocytes.

Adult

Impaired thermoregulation in adults with growth hormone deficiency during heat exposure and exercise.

OBJECTIVE: It has recently been shown that patients with growth hormone deficiency have a reduced sweating capacity. We hypothesize that reduced sweating might affect thermoregulation in growth hormone deficiency patients. In the present study we have examined thermoregulation in growth hormone deficiency patients. DESIGN AND PATIENTS: Six adult growth hormone deficiency patients and six matched controls were exposed to a 90-minute heat period (40 degrees C). On a second day the subjects exercised for 30 minutes under standardized conditions. MEASUREMENTS: On both occasions changes in GH secretion, sweating and temperature were registered. Heat storage and evaporation were calculated from these data. RESULTS: We found that during the moderate heat exposure, evaporation was less (56.7 vs 115.6 W, P = 0.0037) and heat storage greater (60.7 vs 37.0 W, P = 0.025) in growth hormone deficiency patients compared to their matched controls. Two of the six patients reacted with severe clinical symptoms of heat exhaustion, whereas the controls were unaffected. After exercise the patients reached significantly higher core temperatures than their matched controls (38.1 vs 37.8 degrees C, P = 0.0097). CONCLUSIONS: Thus, our findings are indicative of a reduced thermoregulatory function in some patients with GH deficiency.

Adult

Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumour necrosis factor-alpha, interleukin 2 and interferon-gamma.

The present study was designed to examine the effect of physical exercise on production of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). Ten young, healthy volunteers underwent 60-min bicycle exercise at 75% of maximal oxygen uptake (VO2max). Blood samples were collected before and during the last minutes of exercise, as well as 2 h and 24 h later. Blood mononuclear cells (BMNC) were stimulated in vitro with either bacterial lipopolysaccharide or phytohaemagglutinin, and the supernatants were tested for the above-mentioned cytokines using bioassays as well as ELISA techniques. The production of IL-6 increased significantly 2 h after exercise, furthermore the production of IL-1 alpha and IL-1 beta was enhanced, although only borderline significant. TNF-alpha, IL-2 and IFN-gamma did not fluctuate in relation to exercise. The increased amounts of IL-1 and IL-6 in the supernatants generated from a fixed number of BMNC are most likely explained by the increased percentage and absolute number of blood monocytes 2 h after exercise. IL-2 and IFN-gamma are mainly produced by CD4+ and CD16+ cells. During exercise the CD4+ subset decreases, while the CD16+ subset increases. The finding of unchanged production of IL-2 and IFN-gamma was therefore expected.

Adult

Indomethacin in vitro and in vivo abolishes post-exercise suppression of natural killer cell activity in peripheral blood.

The present study was designed to explain the mechanism of the post-exercise down-regulation of human natural killer (NK) cell activity recently described by us. Fifteen young, healthy volunteers underwent 60 min of bicycle exercise at 75% of maximal oxygen uptake (VO2max). Six of the volunteers were exercised twice with an interval of at least one month. At the second exercise test they received oral indomethacin. Blood samples were collected before and during the last minutes of exercise as well as 2 h and 24 h after work. The NK cell activity (lysis fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. During bicycle exercise the percentage of NK cells (CD16+ cells) of mononuclear cells increased significantly but returned to normal within 2 h after exercise. Two hours after exercise, however, increased monocyte cell count and neutrophils were found. The in vitro release of prostaglandin E2 from mononuclear cells was increased. Furthermore, the neutrophil chemiluminescence response was also increased in the 2 h post-exercise period; this response is associated with prostaglandin E2 production by neutrophils. Indomethacin, whether administered in vivo or in vitro, fully restored the suppressed post-exercise NK cell activity. Finally, the NK cell activity of monocyte depleted mononuclear cells did not decrease below basal levels after exercise. These findings strongly indicate that prostaglandins released from monocytes and neutrophils are involved in the post-exercise down-regulation of NK cells.

Adult

Effect of physical exercise on blood mononuclear cell subpopulations and in vitro proliferative responses.

The present study was designed to examine the effect of physical exercise on subsets and proliferative responses of blood mononuclear cells. Sixteen young, healthy volunteers underwent 60 min of bicycle exercise at 75% of maximal oxygen uptake (VO2max). After an interval of at least 1 week, six of the subjects underwent a 60-min back muscle training period at up to 30% of VO2max. Blood samples were collected before and during the last minutes of exercise, as well as 2 and 24 h later. Blood mononuclear cell (BMNC) subpopulations were determined and the proliferative responses after incubation with phytohaemagglutinin (PHA) or purified derivative of tuberculin (PPD), were quantified by [3H]thymidine incorporation. During bicycle exercise the relative blood concentration of T cells (CD3+ cells) declined, mainly due to a fall in T helper cells (CD4+ cells). The natural killer (NK) cell subset (CD16+ cells) increased during work, but reverted after; the monocytes (CD14+ cells) increased 2 h after work, whereas the B-cell subset (CD20+ cells) did not change. BMNC subsets were not significantly changed by back muscle exercise. The PHA-induced proliferative response decreased during bicycle exercise, whereas the PPD-induced response did not change. No significant changes occurred during back muscle exercise. Investigation of subgroups after incubation with [3H]thymidine showed that the proliferative response per CD4+ cell did not change in relation to exercise, but the contribution of the CD4+ subgroup to proliferation declined during bicycle exercise due to the decreased proportion of CD4+ cells. The suppression of the PHA response during bicycle exercise can be explained in part by a relative fall in CD4+ cells. The pool sizes of BMNC subfraction may be elicited by increased catecholamine and cortisol levels.

Adult

Mechanisms of B-lymphocyte suppression induced by acute physical exercise.

Blood mononuclear cells from 20 healthy untrained volunteers were isolated before, during, 2 hr and 24 hr after bicycle exercise at 80% of VO2 max for 1 hr. A reverse plaque forming cell assay was used to investigate B-lymphocyte function. Stimulation with pokeweed mitogen, recombinant interleukin 2 and Epstein-Barr virus resulted in significant decreases in numbers of IgG-, IgM- and IgA-secreting blood cells during as well as 2 hr after exercise, with reversal to pre-exercise values 24 hr later. During and after physical activity we found an unchanged concentration of CD20-positive B lymphocytes suggesting that the suppression of immunoglobulin secreting cells was not due to changes in numbers of B lymphocytes. A decline in CD4/CD8 ratio was measured only during exercise with normalization after exercise. Therefore the B-lymphocyte suppression, most pronounced 2 hr after exercise, was presumably not due to changes in T lymphocytes also indicated in the experiments using EBV-stimulated cultures since EBV acts directly on B lymphocytes. 2 hr after physical activity an increased level of CD14-positive monocytes were observed and the monocytes expressed higher levels of surface HLA-DR during as well as 2 hr after exercise. Addition of indomethacin caused an increased response only in the IL-2 stimulated cultures, suggesting that IL-2-sensitive activated B lymphocytes are downregulated by prostaglandins. Purified B lymphocytes produced plaques only after EBV-stimulation, and in these cultures no exercise-induced suppression was found, likewise suggesting an inhibitory effect of the activated monocytes.

Adult

Interleukin-1-like activities in synovial fluids of patients with rheumatoid arthritis and traumatic synovitis.

Interleukin-1 (Il-1)-like activity in biological fluids was measured by their ability to rectify the Il-1-dependent lymphokine production of highly purified T lymphocytes to a recall antigen. Il-1-like activity was found in 9 of 11 synovial fluid (SF) specimens from patients with rheumatoid arthritis (RA) but only in 2 of 11 paired RA sera. In traumatic synovitis, low Il-1-like activity was recorded in 5 of 9 SF specimens, and a similar low activity was found in sera of 4 of these patients. The Il-1-like activity was partly absorbed by an anti-Il-1 antibody. The presence of Il-1 in the SF of patients with RA suggests in vivo activation of monocytes/macrophages.

Adsorption

Maximum oxygen consumption rate and dihydrogenated ergot alkaloids in humans.

The relationship of maximal oxygen uptake (VO2 max) with dihydrogenated ergot alkaloids was investigated in twelve young men. They were subjected to graded bicycle exercise with work loads corresponding to 75% and 120% of the load necessary to elicit VO2 max. The exercise tests were performed after intravenous administration of 2 mg dihydroergostin (DE-145) as well as after saline as control, both preparations were given double-blind. VO2 max averaged (SD) 3.36 (0.41) 1/min and no significant difference was disclosed between the DE-145 and the control situation. Normal relationships were observed between VO2 and work load, ventilation, heart rate, cardiac output, central venous pressure and acid-base data, and these relations were unaffected by DE-145 administration. Nausea was constantly seen in all subjects tested with DE-145. It is concluded, that the present dose of DE-145 has no influence on the functional capacity of the oxygen transporting system in sedentary young men.

Adult

Synovial fluid and blood monocytes/macrophages in rheumatoid arthritis. Influence on polyclonal activation of autologous B lymphocytes.

The regulatory role of synovial fluid monocytes/macrophages from patients with rheumatoid arthritis in terms of B lymphocyte activation was evaluated by a reverse haemolytic plaque-forming cell (PFC) assay. Macrophage-depleted blood mononuclear cells (BMC) failed to respond to pokeweed mitogen (PWM). With autologous synovial fluid macrophages added, the PFC responses of macrophage-depleted BMC increased, and optimal concentration for full restoration of the PFC responses ranged from 8 to 35%. Synovial fluid mononuclear cells (SMC) as well as macrophage-depleted SMC were not able to respond to PWM. Addition of irradiated autologous blood macrophages to SMC did not increase the SMC PFC responses. It is concluded that the regulatory properties of synovial fluid macrophages do not explain the low PFC response of SMC to PWM.

Adult

Physical training in bronchial asthma.

Physical exercise is advocated as an important form of preventative medicine and in the treatment of various cardiovascular diseases. This review looks at whether a similar approach may be of value in chronic obstructive lung disease (COLD). Few studies have been properly controlled and outcome measures are not well defined. However, it is clear that exercise is safe and increases work capacity and sense of well being.

Asthma

Short-term physical training in bronchial asthma.

The effect of two types of physical training on patients with perennial asthma were compared in a blind, controlled, randomized study. Eleven of 27 adults with asthma performed a physical training programme which did not change their oxygen consumption (control group). The remaining 16 asthmatics performed a physical training programme which improved their maximal oxygen consumption (training group). Both of the training programmes were performed for 1 hour, twice a week during a period of 2 months. No complications were reported during the performance of the training programmes. The doses of all medicines apart from beta 2-agonist aerosol were unchanged during the training period. The patients inhaled beta 2-agonist aerosol if their peak expiratory flow (PEF) was less than 60% of their maximal PEF. The training group decreased their use of aerosol from an average of 4.94 puffs per day to 3.41 puffs per day (P less than 0.05). The control group did not change their use of beta 2-agonist aerosol significantly. It is concluded that physical exercise which improves the maximal oxygen consumption decreases the use of beta 2-agonist spray and that heavy exercise is well tolerated by asthmatics.

Adrenergic beta-Agonists