Substantial elevation of interleukin-6 concentration in peritendinous tissue, in contrast to muscle, following prolonged exercise in humans

Abstract

Plasma interleukin-6 (IL-6) concentration has been shown to increase with exercise and various cell types and tissues have been suggested to be responsible for this increase. At present no studies have measured the interstitial concentration of IL-6 in skeletal muscle and connective tissue. The present study represents the first attempt to simultaneously measure IL-6 in plasma, skeletal muscle and peritendinous connective tissue in response to prolonged exercise. Six healthy well-trained volunteers completed a 36 km run (flat, 12 km h(-1)). IL-6 was measured before, 2 h post-exercise and 24 h, 48 h, 72 h and 96 h post-exercise in both the medial gastrocnemius muscle (not measured at rest due to risk of disabling the subsequent exercise, and 24 h and 72 h post-exercise) and the peritendinous tissue around the Achilles tendon using microdialysis catheters with a high molecular mass cut-off value (3000 kDa). The plasma concentration of IL-6 was measured simultaneously, and in addition every hour during the exercise, by enzyme-linked immunosorbent assay (ELISA). The plasma concentration of IL-6 was found to increase throughout the exercise, reaching peak values immediately after completion of the run (50-fold increase). Using the microdialysis technique, the interstitial concentration of IL-6 was found to increase dramatically from 0 +/- 0 pg ml(-1) to 3618 +/- 1239 pg ml(-1) in the peritendinous tissue in the hours following the exercise. The pattern of changes was similar in plasma and peritendinous tissue, although approximately 100-fold higher in the latter. For comparison the interstitial muscle concentration was found to be 465 +/- 176 pg ml(-1) when measured 2 h post-exercise and 223 +/- 113 pg ml(-1) and 198 +/- 96 pg ml(-1) 48 h and 96 h post-exercise, respectively. The present study demonstrates that the connective tissue around the human Achilles tendon produces significant amounts of IL-6 in response to prolonged physical activity, which might contribute to the exercise-induced increase in IL-6 found in plasma.

Figure 1. Plasma IL-6 data from six healthy well-trained males measured before, every hour during the 3 h run, immediately after, and during the 4 days following the exercise

Plasma IL-6 concentration is shown to increase throughout the exercise bout, peaking at the end of the bout. The concentration diminished during the hour following the run and was found to return to pre-exercising level 48 h post-exercise. Data are given as means ± s.e.m.; *P < 0.05 vs. before.

Figure 2. IL-6 data measured in the medial gastrocnemius muscle in six healthy well-trained males measured immediately after, and during the 4 days following the exercise

No measurements were performed in the muscle before exercise due to the risk of compromising the ability of the skeletal muscles to perform the 36 km run. The concentration of IL-6 in the muscle was found to decrease during the days following the exercise, but this was not significant. Data are given as means ± s.e.m.

Figure 3. Interstitial concentration of IL-6 in the peritendinous tissue around the Achilles tendon measured before, immediately after and during the 4 days following the exercise in six healthy well-trained males

The concentration of IL-6 around the Achilles tendon was close to zero before exercise indicating that the insertion of the microdialysis catheters did not induce a release of IL-6 from the tissue. As a consequence of the prolonged exercise IL-6 was found to rise dramatically, reaching a concentration beyond what has previously been reported. During the days following the exercise IL-6 concentration decreased, reaching levels not significantly different from pre-exercise levels after 72 h. Data are given as means ± s.e.m.; *P < 0.05 vs. before.