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Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle.
J Physiol. 2004 Jul 15; 558(Pt 2):633-45.JP

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 exercise-induced 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 single-blind 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-alpha-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(2alpha), 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 approximately 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), CI 13.8-29.4 pg ml(-1), at 3.5 h, P < 0.05 between groups). 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.

Authors+Show Affiliations

Copenhagen Muscle Research Centre, Copenhagen, Denmark. cfischer@rh.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15169848

Citation

Fischer, Christian P., et al. "Supplementation With Vitamins C and E Inhibits the Release of Interleukin-6 From Contracting Human Skeletal Muscle." The Journal of Physiology, vol. 558, no. Pt 2, 2004, pp. 633-45.
Fischer CP, Hiscock NJ, Penkowa M, et al. Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle. J Physiol. 2004;558(Pt 2):633-45.
Fischer, C. P., Hiscock, N. J., Penkowa, M., Basu, S., Vessby, B., Kallner, A., Sjöberg, L. B., & Pedersen, B. K. (2004). Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle. The Journal of Physiology, 558(Pt 2), 633-45.
Fischer CP, et al. Supplementation With Vitamins C and E Inhibits the Release of Interleukin-6 From Contracting Human Skeletal Muscle. J Physiol. 2004 Jul 15;558(Pt 2):633-45. PubMed PMID: 15169848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle. AU - Fischer,Christian P, AU - Hiscock,Natalie J, AU - Penkowa,Milena, AU - Basu,Samar, AU - Vessby,Bengt, AU - Kallner,Anders, AU - Sjöberg,Lars-Börje, AU - Pedersen,Bente K, Y1 - 2004/05/28/ PY - 2004/6/1/pubmed PY - 2005/1/26/medline PY - 2004/6/1/entrez SP - 633 EP - 45 JF - The Journal of physiology JO - J Physiol VL - 558 IS - Pt 2 N2 - 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 exercise-induced 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 single-blind 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-alpha-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(2alpha), 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 approximately 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), CI 13.8-29.4 pg ml(-1), at 3.5 h, P < 0.05 between groups). 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. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/15169848/Supplementation_with_vitamins_C_and_E_inhibits_the_release_of_interleukin_6_from_contracting_human_skeletal_muscle_ L2 - https://doi.org/10.1113/jphysiol.2004.066779 DB - PRIME DP - Unbound Medicine ER -