The present study investigates to what extent and by which time course prolonged strenuous exercise influences the plasma concentration of pro‐inflammatory and inflammation responsive cytokines as well as cytokine inhibitors and anti‐inflammatory cytokines. Ten male subjects (median age 27.5 years, range 24–37) completed the Copenhagen Marathon 1997 (median running time 3:26 (h:min), range 2:40–4:20). Blood samples were obtained before, immediately after and then every 30 min in a 4 h post‐exercise recovery period. The plasma concentrations of tumour necrosis factor (TNF)α, interleukin (IL)‐1β, IL‐6, IL‐1ra, sTNF‐r1, sTNF‐r2 and IL‐10 were measured by enzyme‐linked immunosorbent assay (ELISA). The highest concentration of IL‐6 was found immediately after the race, whereas IL‐1ra peaked 1 h post exercise (128‐fold and 39‐fold increase, respectively, as compared with the pre‐exercise values). The plasma level of IL‐1β, TNFα, sTNF‐r1 and sTNF‐r2 peaked in the first hour after the exercise (2.1‐, 2.3‐, 2.7‐ and 1.6‐fold, respectively). The plasma level of IL‐10 showed a 27‐fold increase immediately post exercise. In conclusion, strenuous exercise induces an increase in the pro‐inflammatory cytokines TNFα and IL‐1β and a dramatic increase in the inflammation responsive cytokine IL‐6. This is balanced by the release of cytokine inhibitors (IL‐1ra, sTNF‐r1 and sTNF‐r2) and the anti‐inflammatory cytokine IL‐10. The study suggests that cytokine inhibitors and anti‐inflammatory cytokines restrict the magnitude and duration of the inflammatory response to exercise.

This study was performed to test the hypothesis that inflammatory cytokines are produced in skeletal muscle in response to prolonged intense exercise. Muscle biopsies and blood samples were collected from runners before, immediately after, and 2 h after a marathon race. The concentration of interleukin (IL)‐6 protein in plasma increased from 1.5 ± 0.7 to 94.4 ± 12.6 pg ml−1 immediately post‐exercise and to 22.1 ± 3.8 pg ml−1 2 h post‐exercise. IL‐1 receptor antagonist (IL‐1ra) protein in plasma increased from 123 ± 23 to 2795 ± 551 pg ml−1, and increased further to 4119 ± 527 pg ml−1 2 h post‐exercise. The comparative polymerase chain reaction technique was used to evaluate mRNA for IL‐6, IL‐1ra, IL‐1β and tumour necrosis factor (TNF)‐α in skeletal muscle and blood mononuclear cells (BMNC) (n= 8). Before exercise, mRNA for IL‐6 could not be detected either in muscle or in BMNC, and was only detectable in muscle biopsies (5 out of 8) after exercise. Increased amounts of mRNA for IL‐1ra were found in two muscle biopsies and five BMNC samples, and increased amounts of IL‐1β mRNA were found in one muscle and four BMNC samples after exercise. TNF‐α mRNA was not detected in any samples. This study suggests that exercise‐induced destruction of muscle fibres in skeletal muscles may trigger local production of IL‐6, which stimulates the production of IL‐1ra from circulating BMNC.

The present study explored the hypothesis that interleukin‐6 (IL‐6) might be locally produced in response to skeletal muscle contractions and whether the production might reflect the type of muscle contraction performed. Rats were anaesthetized and the calf muscles of one limb were stimulated electrically for concentric or eccentric contractions (4 × 10 contractions with 1 min of rest between the 4 series, 100 Hz). The contralateral muscles served as unstimulated controls. The mRNA levels for IL‐6, the glucose transport protein GLUT‐4 and β‐actin in the rat muscles (white and red gastrocnemius and soleus) were quantified by quantitative competitive RT‐PCR. The IL‐6 mRNA level, measured 30 min after the stimulation, increased after both eccentric and concentric contractions and there were no significant differences in IL‐6 mRNA levels between the different muscle fibre types. No significant increase in IL‐6 mRNA level was seen in the unstimulated contralateral muscle fibres. No increase in GLUT‐4 mRNA level was detected, indicating that the increase in IL‐6 mRNA level was not due to general changes in transcription. We conclude that IL‐6 is locally produced after muscle contraction, with no significant differences between different muscle fibre types. This local production of IL‐6 is not due to general changes in transcription, since no changes in the level of GLUT‐4 mRNA were found. The fact that increased IL‐6 mRNA levels were seen after both concentric and eccentric contractions indicates that the production of IL‐6 is not solely due to muscle damage, seen primarily after eccentric exercise.

Studies in rats suggest that increases in fatty acid oxidation in skeletal muscle during exercise are related to the phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), and secondary to this, a decrease in the concentration of malonyl-CoA. Studies in human muscle have not revealed a consistent decrease in the concentration of malonyl-CoA during exercise; however, measurements of ACC activity have not been reported. Thus, whether the same mechanism operates in human muscle in response to physical activity remains uncertain. To investigate this question, ACC was immunoprecipitated from muscle of human volunteers and its activity assayed in the same individual at rest and after one-legged kneeextensor exercise at 60, 85, and 100% of knee extensor VO 2max . ACC activity was diminished by 50-75% during exercise with the magnitude of the decrease generally paralleling exercise intensity. Treatment of the immunoprecipitated enzyme with protein phosphatase 2A restored activity to resting values, suggesting the decrease in activity was due to phosphorylation. The measurement of malonyl-CoA in the muscles revealed that its concentration is 1/10 of that in rats, and that it is diminished (12-17%) during the higher-intensity exercises. The respiratory exchange ratio increased with increasing exercise intensity from 0.84 ± 0.02 at 60% to 0.99 ± 0.04 at 100% VO 2max . Calculated rates of whole-body fatty acid oxidation were 121 mg/min at rest and 258 ± 35, 264 ± 63, and 174 ± 76 mg/min at 60, 85, and 100% VO 2max , respectively. The results show that ACC activity, and to a lesser extent malonyl-CoA concentration, in human skeletal muscle decrease during exercise. Although these changes may contribute to the increases in fat oxidation from rest to exercise, they do not appear to explain the shift from mixed fuel to predominantly carbohydrate utilization when exercise intensity is increased. Diabetes 49:1295-1300, 2000 P hysical activity is associated with substantial increases in both fatty acid and carbohydrate oxidation in skeletal muscle, with the relative use of the 2 fuels varying with exercise intensity (1). Thus, in overnight-fasted humans, during low-intensity exercise (30-40% VO 2max ), fatty acids are the principal oxidative substrate, whereas during somewhat more intense exercise (60-70% VO 2max ), the absolute rates of both fatty acid and carbohydrate oxidation are higher, but the oxidation of fatty acids relative to carbohydrate is decreased. Furthermore, during very intense (≥90% VO 2max ) versus moderate-intensity exercise, carbohydrate oxidation is still further increased, and even the rate of fatty acid oxidation may be diminished.Studies in both rats (2-6) and humans (7,8) indicate that the rate of carbohydrate oxidation in muscle is elevated during exercise by a coordinated series of events that lead to increases in glucose transport, glycogenolysis, glycolysis, and pyruvate dehydrogenase activity. In contrast, the mechanism by which fatty acid oxidation is increased is less clear. In rats, a rea...

1. Eccentric exercise causes impaired postexercise glycogen resynthesis. To study whether changes in muscle concentration of the glucose transporter (GLUT4) protein might be involved, seven healthy young men performed one-legged eccentric exercise by resisting knee flexion enforced by a motor-driven device. 2. The GLUT4 protein concentration in the exercised and in the control thigh was unchanged immediately after exercise. On days 1 and 2 after exercise, the GLUT4 protein concentration in the exercised muscle was 68 + 10 and 64 + 10% (means + S.E.M.; P < 0 05), respectively, of the concentration in the control muscle, and had returned to control values on days 4 and 7.3. The muscle glycogen concentration decreased from 404 + 44 to 336 + 44 mmol (kg dry wtf1 (P < 0 05) during exercise. The glycogen concentration remained significantly lower than in the control thigh on days 1 and 2 after exercise but on days 4 and 7 no differences were found. 4. Although no cause-effect relationship was established, these findings may suggest that decreased muscle concentrations of GLUT4 protein, and, hence, a decreased rate of glucose transport into muscle cells, may concentration seen after eccentric exercise.Eccentric exercise has been shown to cause muscle damage and impaired postexercise glycogen resynthesis (O'Reilly,