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. doi: 10.1113/jphysiol.2004.066779. Epub 2004 May 28.


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.

Publication types

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

MeSH terms

  • Adult
  • Antioxidants / administration & dosage*
  • Antioxidants / metabolism
  • Ascorbic Acid / administration & dosage*
  • Ascorbic Acid / blood
  • Blood Glucose
  • C-Reactive Protein / metabolism
  • Exercise / physiology
  • Gene Expression / drug effects
  • Humans
  • Hydrocortisone / blood
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Lipid Peroxidation / drug effects
  • Male
  • Muscle Contraction / physiology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / physiology
  • Sialoglycoproteins / blood
  • Vitamin E / administration & dosage*
  • Vitamin E / blood


  • Antioxidants
  • Blood Glucose
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Sialoglycoproteins
  • Vitamin E
  • C-Reactive Protein
  • Ascorbic Acid
  • Hydrocortisone