Abstract
It has been reported that IL-6 knockout mice (IL-6−/−) possess lower endurance capacity than wild type mice (WT), however the underlying mechanism is poorly understood. The aim of the present work was to examine whether reduced endurance running capacity in IL-6−/− mice is linked to impaired maximal oxygen uptake (V′O2max), decreased glucose tolerance, endothelial dysfunction or other mechanisms. Maximal running velocity during incremental running to exhaustion was significantly lower in IL-6−/− mice than in WT mice (13.00±0.97 m.min−1 vs. 16.89±1.15 m.min−1, P<0.02, respectively). Moreover, the time to exhaustion during running at 12 m.min−1 in IL-6−/− mice was significantly shorter (P<0.05) than in WT mice. V′O2max in IL-6−/− (n = 20) amounting to 108.3±2.8 ml.kg−1.min−1 was similar as in WT mice (n = 22) amounting to 113.0±1.8 ml.kg−1.min−1, (P = 0.16). No difference in maximal COX activity between the IL-6−/− and WT mice in m. soleus and m. gastrocnemius was found. Moreover, no impairment of peripheral endothelial function or glucose tolerance was found in IL-6−/− mice. Surprisingly, plasma lactate concentration during running at 8 m.min−1 as well at maximal running velocity in IL-6−/− mice was significantly lower (P<0.01) than in WT mice. Interestingly, IL-6−/− mice displayed important adaptive mechanisms including significantly lower oxygen cost of running at a given speed accompanied by lower expression of sarcoplasmic reticulum Ca2+-ATPase and lower plasma lactate concentrations during running at submaximal and maximal running velocities. In conclusion, impaired endurance running capacity in IL-6−/− mice could not be explained by reduced V′O2max, endothelial dysfunction or impaired muscle oxidative capacity. Therefore, our results indicate that IL-6 cannot be regarded as a major regulator of exercise capacity but rather as a modulator of endurance performance. Furthermore, we identified important compensatory mechanism limiting reduced exercise performance in IL-6−/− mice.
Highlights
It is widely recognized that interleukins are secreted by macrophages and lymphocytes to coordinate the response of the immune system to injury and infection [1]
We examined whether lower exercise tolerance in IL-62/2 could be linked to alterations in glucose tolerance, endothelial function or changes in locomotor muscle profile including activities of mitochondrial enzymes or expression of sarcoplasmic reticulum Ca2+-ATPase (SERCA) and uncoupling protein-3 (UCP-3)
IL-62/2 and wild type mice (WT) mice were subjected to maximal incremental exercise treadmill test to assess their maximal running velocity in this protocol which was by about 23% lower for IL-6 knockouts (13.0060.97 m.min21, n = 12) when compared with WT controls (16.961.2 m.min21, n = 12); P,0.02) (Figure 1A)
Summary
It is widely recognized that interleukins are secreted by macrophages and lymphocytes to coordinate the response of the immune system to injury and infection [1]. The data concerning regulation of the whole-body glucose and lipid metabolism in IL-62/2 animals are not so evident since one group referred to age-related insulin resistance and weight gain of IL-62/2 mice [10,11] while the other did not confirm this observation [12,13]. These data cannot explain the reduced exercise performance of IL-62/2 mice. Despite previous works, the mechanisms underlying impairment of exercise tolerance in IL-62/2 animals are still not known
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