To examine the plasma interleukin (IL)-6 response in elderly (E) and young (Y) humans, 10 E and 10 Y subjects completed 60 min of eccentric lower limb exercise at the same relative oxygen uptake. Plasma IL-6 was measured before, immediately after, and 5 days into recovery from exercise, as were the biochemical markers of muscle damage, creatine kinase (CK), and myoglobin. In both groups, IL-6 increased (P < 0.05) immediately after exercise and peaked 4 h after exercise at 4.35 +/- 1.7 vs. 5.05 +/- 3.17 pg/ml for E and Y subjects, respectively. However, the increase in IL-6 in both groups was modest relative to the increases in CK peaking at 539 +/- 413 vs. 10,301 +/- 5,863 U/l for E and Y subjects, respectively. In addition, the increase in IL-6 was less pronounced (P < 0.05) in E subjects compared with Y subjects. These results suggest that IL-6 increases progressively after eccentric exercise, suggesting that this increase is related to muscle damage. However, the modest increase in IL-6, despite large increases in CK, suggests that the IL-6 response to muscle damage does not make an important contribution to the large increase in IL-6 observed during concentric exercise of long duration. Our data also suggest that aging may be associated with impaired repair mechanisms for exercise-induced muscle damage.

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.

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.

The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis. Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects.

The aim of the present study was to investigate whether fish oil supplementation was able to modulate the acute-phase response to strenuous exercise. Twenty male runners were randomized to receive supplementation (n = 10) with 6.0 g fish oil daily, containing 3.6 g n-3 polyunsaturated fatty acids (PUFA), for 6 wk or to receive no supplementation (n = 10) before participating in The Copenhagen Marathon 1998. Blood samples were collected before the race, immediately after, and 1.5 and 3 h postexercise. The fatty acid composition in blood mononuclear cells (BMNC) differed between the fish oil-supplemented and the control group, showing incorporation of n-3 PUFA and less arachidonic acid in BMNC in the supplemented group. The plasma levels of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta(1) peaked immediately after the run, the increase being 3-, 92-, and 1.1-fold, respectively, compared with resting samples. The level of interleukin-1 receptor antagonist peaked 1.5 h after exercise, with the increase being 87-fold. However, the cytokine levels did not differ among the two groups. Furthermore, supplementation with fish oil did not influence exercise-induced increases in leucocytes and creatine kinase. In conclusion, 6 wk of fish oil supplementation had no influence on the acute-phase response to strenuous exercise.

Exercise induces a post-exercise decline in the number of circulating lymphocytes. The aim of the present study was to investigate whether strenuous exercise induces lymphocyte apoptosis and generation of reactive oxygen species. Eleven healthy male subjects exercised for 2.5 h on a treadmill. Apoptotic lymphocytes were defined by being annexin positive and 7-aminoactinomycin-D negative. Measurement of F(2)-isoprostanes was used as a marker of oxidant stress in vivo. An increase (60%, P<0.05) in the percentage of apoptotic circulating lymphocytes was found 2 h post-exercise, whereas the total number of apoptotic cells did not change in relation to exercise. The concentration of plasma F(2)-isoprostanes increased approximately 1.6-fold in response to exercise, but declined towards pre-exercise values within the 1st h of recovery. The plasma concentrations of adrenaline, noradrenaline and cortisol increased during exercise. In conclusion, the results of the present study demonstrate that even in a study design in which high levels of apoptosis-inducing factors are generated, such as cortisol and isoprostanes, lymphocyte apoptosis does not contribute to post-exercise lymphocytopenia.

No abstract

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.