Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content

Abstract

1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from contracting muscle is linked to the intramuscular glycogen availability. 2. Seven men performed 5 h of a two-legged knee-extensor exercise, with one leg with normal, and one leg with reduced, muscle glycogen content. Muscle biopsies were obtained before (pre-ex), immediately after (end-ex) and 3 h into recovery (3 h rec) from exercise in both legs. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery. 3. Pre-exercise glycogen content was lower in the glycogen-depleted leg compared with the control leg. Intramuscular IL-6 mRNA levels increased with exercise in both legs, but this increase was augmented in the leg having the lowest glycogen content at end-ex. The arterial plasma concentration of IL-6 increased from 0.6 +/- 0.1 ng x l(-1) pre-ex to 21.7 +/- 5.6 ng x l(-1) end-ex. The depleted leg had already released IL-6 after 1 h (4.38 +/- 2.80 ng x min(-1) (P < 0.05)), whereas no significant release was observed in the control leg (0.36 +/- 0.14 ng x min(-1)). A significant net IL-6 release was not observed until 2 h in the control leg. 4. This study demonstrates that glycogen availability is associated with alterations in the rate of IL-6 production and release in contracting skeletal muscle.

Figure 1

The kicking profile for one subject for a glycogen-depleted leg and a control leg, respectively, at a given time point during the knee-extensor exercise. This was measured by a strain gauge and visualized on a computer. Note that the kicking rate is 60 kicks min⁻¹.

Figure 4. Accumulation of plasma creatine kinase

Data are presented as means and s.e.m. Day-1 is obtained before glycogen depletion and pre before the two-legged knee-extensor exercise, n = 7. * Significant difference from pre value (P < 0.05). Pre values did not differ from day-1 values.

Figure 3. Glycogen depletion

Net glucose uptake by a glycogen-depleted and a control leg, respectively (Fick's principle: blood flow times a-fv differences) measured before and every hour during knee-extensor exercise and at the cession of the 3 h recovery, n = 7. Data are presented as means and s.e.m.* Significant difference from pre-ex (P < 0.05), § significant difference between legs (P < 0.05).

Figure 2. Muscle glycogen content

Muscle glycogen content in a glycogen-depleted and a control leg, respectively, before and after knee-extensor exercise and 3 h into recovery, n = 7. Data are presented as means and s.e.m.* Significant difference from pre-ex (P < 0.05), § significant difference between legs (P < 0.05).

Figure 5

IL-6 data for 7 male subjects measured before and every hour during knee-extensor exercise and recovery. Data are presented as means and s.e.m.A, arterial IL-6 plasma concentrations. B, a-fv differences for a glycogen-depleted and a control leg, respectively. C, net release of IL-6 from a glycogen-depleted and a control leg, respectively (Fick's principle: blood flow × a-fv differences). * Significant difference from pre-ex (P < 0.05), § significant difference between legs (P < 0.05).

Figure 7

IL-6 mRNA in a glycogen-depleted leg and a control leg after knee-extensor exercise and 3 h into recovery measured by real time PCR, n = 7. Data are presented as means and s.e.m.* Significant difference from pre-ex (P < 0.05).

Figure 6

Blood flow in a glycogen-depleted leg and a control leg, respectively, measured before and every hour during knee-extensor exercise and recovery, n = 7. Data are presented as means and s.e.m.* Significant difference from pre-ex (P < 0.05).