title: Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans.
abstract: During "nondamaging" exercise, skeletal muscle markedly releases interleukin (IL)-6, and it has been suggested that one biological role of this phenomenon is to inhibit the production of tumor necrosis factor (TNF)- alpha, which is known to cause pathogenesis such as insulin resistance and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli lipopolysaccharide endotoxin (0.06 ng/kg) i.v. to induce low-grade inflammation. In CON, plasma TNF-alpha increased significantly in response to endotoxin. In contrast, during EX, which resulted in elevated IL-6, and rhIL-6, the endotoxin-induced increase in TNF-alpha was totally attenuated. In conclusion, physical exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced by and released from exercising muscles.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Starkie
authors.forename: Sisse Rye
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: Sune
authors.initials: S
authors.lastname: Jauffred
authors.forename: Mark
authors.initials: M
authors.lastname: Febbraio
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000704:Analysis of Variance; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D011187:Posture / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha