Endurance training enhances skeletal muscle interleukin-15 in human male subjects.

Regular endurance exercise promotes metabolic and oxidative changes in skeletal muscle. Overexpression of interleukin-15 (IL-15) in mice exerts similar metabolic changes in muscle as seen with endurance exercise. Muscular IL-15 production has been shown to increase in mice after weeks of regular endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer cycling exercise five times per week with plasma and biopsies before and after the intervention, and (2) 3 h of ergometer cycling exercise with plasma and biopsies before and after the exercise bout and well into recovery. We measured changes in plasma IL-15, muscle IL-15 mRNA and IL-15 protein. Twelve weeks of regular endurance training induced a 40% increase in basal skeletal muscle IL-15 protein content (p < 0.01), but with no changes in either muscle IL-15 mRNA or plasma IL-15 levels. However, an acute bout of 3-h exercise did not show significant changes in muscle IL-15 or plasma IL-15 levels. The induction of muscle IL-15 protein in humans following a regular training period supports previous findings in mice and emphasizes the hypothesis of IL-15 taking part in skeletal muscle adaptation during training.

Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle.

The leukaemia inhibitory factor (LIF) belongs to the interleukin (IL)-6 cytokine superfamily and is constitutively expressed in skeletal muscle. We tested the hypothesis that LIF expression in human skeletal muscle is regulated by exercise. Fifteen healthy young male volunteers performed either 3 h of cycle ergometer exercise at approximately 60% of VO2,max(n = 8) or rested (n = 7). Muscle biopsies were obtained from the vastus lateralis prior to exercise, immediately after exercise, and at 1.5, 3, 6 and 24 h post exercise. Control subjects had biopsy samples taken at the same time points as during the exercise trial. Skeletal muscle LIF mRNA increased immediately after the exercise and declined gradually during recovery. However, LIF protein was unchanged at the investigated time points. Moreover, we tested the hypothesis that LIF mRNA and protein expressions are modulated by calcium (Ca(2+)) in primary human skeletal myocytes. Treatment of myocytes with the Ca(2+) ionophore, ionomycin, for 6 h resulted in an increase in both LIF mRNA and LIF protein levels. This finding suggests that Ca(2+) may be involved in the regulation of LIF in endurance-exercised skeletal muscle. In conclusion, primary human skeletal myocytes have the capability to produce LIF in response to ionomycin stimulation and LIF mRNA levels increase in skeletal muscle following concentric exercise. The finding that the increase in LIF mRNA levels is not followed by a similar increase in skeletal muscle LIF protein suggests that other exercise stimuli or repetitive stimuli are necessary in order to induce a detectable accumulation of LIF protein.

Exercise induces interleukin-8 receptor (CXCR2) expression in human skeletal muscle.

Exercise induces a marked increase in interleukin-8 (IL-8) mRNA and protein expression within skeletal muscle fibres. Interleukin-8 belongs to a subfamily of CXC chemokines containing a Glu-Leu-Arg (ELR) motif. CXC chemokines with ELR motifs are potent angiogenic factors in vivo, and IL-8 has been shown to act as an angiogenic factor in human microvascular endothelial cells by binding to the CXC receptor 2 (CXCR2). In the present study, we examined the expression of the interleukin-8 receptor CXCR2 in human skeletal muscle biopsies after concentric exercise. Healthy volunteers were randomized to either 3 h of cycle ergometer exercise at 60% of maximum oxygen uptake (n = 8) or rest (n = 7). Muscle biopsy samples were obtained from the vastus lateralis before exercise (0 h), immediately after exercise (3 h), and at 4.5, 6, 9 and 24 h. Skeletal muscle CXCR2 mRNA increased significantly in response to exercise (3 and 4.5 h) when compared with pre-exercise samples. Expression of the CXCR2 protein was low in skeletal muscle biopsies before exercise and at the end of the exercise period (3 h). However, at 4.5-9 h, an increase in CXCR2 protein was seen in the vascular endothelium, and also slightly within the muscle fibres, as determined by immunohistochemistry. The present study demonstrates that concentric exercise induces CXCR2 mRNA and protein expression in the vascular endothelial cells of the muscle fibres. These findings suggest that muscle-derived IL-8 may act locally to stimulate angiogenesis through CXCR2 receptor signalling.