title: 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 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.affiliation: Copenhagen Muscle Research Centre, Copenhagen, Denmark. cfischer@rh.dk
authors.forename: Christian P
authors.initials: CP
authors.lastname: Fischer
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Hiscock
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
authors.forename: Bengt
authors.initials: B
authors.lastname: Vessby
authors.forename: Anders
authors.initials: A
authors.lastname: Kallner
authors.forename: Lars-Börje
authors.initials: LB
authors.lastname: Sjöberg
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000097:blood; D001786:Blood Glucose; D002097:C-Reactive Protein / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D012795:Sialoglycoproteins / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D012795:Sialoglycoproteins; D014810:Vitamin E; D002097:C-Reactive Protein; D001205:Ascorbic Acid; D006854:Hydrocortisone