Supplementation with vitamins C and E inhibits the release of interleukin‐6 from contracting human skeletal muscle

Abstract

Contracting human skeletal muscle is a major contributor to the exercise-induced increase of plasma interleukin-6 (IL-6). Although antioxidants have been shown to attenuate the exerciseinduced increase of plasma IL-6, it is unknown whether antioxidants inhibit transcription, translation or translocation of IL-6 within contracting human skeletal muscle. Using a singleblind placebo-controlled design with randomization, young healthy men received an oral supplementation with either a combination of ascorbic acid (500 mg day −1 ) and RRR-α-tocopherol (400 i.u. day −1 ) (Treatment, n = 7), or placebo (Control, n = 7). After 28 days of supplementation, the subjects performed 3 h of dynamic two-legged knee-extensor exercise at 50% of their individual maximal power output. Muscle biopsies from vastus lateralis were obtained at rest (0 h), immediately post exercise (3 h) and after 3 h of recovery (6 h). Leg blood flow was measured using Doppler ultrasonography. Plasma IL-6 concentration was measured in blood sampled from the femoral artery and vein. The net release of IL-6 was calculated using Fick's principle. Plasma vitamin C and E concentrations were elevated in Treatment compared to Control. Plasma 8-iso-prostaglandin F 2α , a marker of lipid peroxidation, increased in response to exercise in Control, but not in Treatment. In both Control and Treatment, skeletal muscle IL-6 mRNA and protein levels increased between 0 and 3 h. In contrast, the net release of IL-6 from the leg, which increased during exercise with a peak at 3.5 h in Control, was completely blunted during exercise in Treatment. The arterial plasma IL-6 concentration from 3 to 4 h, when the arterial IL-6 levels peaked in both groups, was ∼50% lower in the Treatment group compared to Control (Treatment versus Control: 7.9 pg ml −1 , 95% confidence interval (CI) 6.0-10.7 pg ml −1 ,versus 19.7 pg ml −1 ,CI13.8-29.4 pg ml −1 ,at3.5 h,P < 0.05betweengroups). Moreover, plasma interleukin-1 receptor antagonist (IL-1ra), C-reactive protein and cortisol levels all increased after the exercise in Control, but not in Treatment. In conclusion, our results show that supplementation with vitamins C and E attenuated the systemic IL-6 response to exercise primarily via inhibition of the IL-6 protein release from the contracting skeletal muscle per se.

Nutritional modulation of exercise-induced immunodepression in athletes: a systematic review and meta-analysis

“…In two additional interventions, a mixture of plant sterols and sterolins attenuated the cortisol increase (Bouic et al, 1999) and a 1.2% glutamine drink had no effect compared with placebo (Walsh et al, 2000) in runners. An inhibitory effect of combined vitamin C and vitamin E supplementation (for 4 weeks) on plasma IL-6 and cortisol responses to prolonged exercise has been reported, although in physically active non-athletes (Fischer et al, 2004). Acute supplementation with zinc and vitamin E did not have an effect on the cortisol response to exercise in eumenorrheic runners (Singh et al, 1999).…”

Efeito do exercício no sistema imune: resposta, adaptação e sinalização celular

“…On the other hand, running, which involves a greater quantity of muscle groups, is the exercise modality in which the most remarkable IL-6 increase was observed 28 . The serum level peak of this cytokine was observed at the end of the exercise performance or in a short period of time after it, followed by a rapid decrease that returned to the pre--exercise period levels 35 . Thus, the combination between modality, intensity and duration of physical activity determine the magnitude of the plasma concentration of exercise-induced IL-6 28 .…”

“…However, it presents an indirect anti-inflammatory action by the stimulation of the synthesis of IL-1ra and IL-10 27,28 . This cytokine has been named myocin, since the contraction of skeletal muscles during prolonged exercises releases large concentrations of it into the circulation [28][29][30][31][32][33][34][35] . The IL-8 and IL-15 have also been described by some studies as myocins 28,32,36,37 (table1).…”

Effects of Physical Exercise on Inflammatory Markers of Atherosclerosis

“…The peak IL-6 level is reached at the end of the exercise or shortly thereafter [155], followed by a rapid decrease towards pre-exercise levels. Young healthy individuals performed 3 h of dynamic two-legged knee-extensor exercise at 50% of their individual maximal power output.…”