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Age-related loss of associations between acute exercise-induced IL-6 and oxidative stress

¹Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy; ²Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts; ³School of Allied Health Sciences, Medical College of Georgia, Augusta, Georgia; ⁴Saga Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd., Saga, Japan; and ⁵Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Boston, Massachusetts

Submitted 4 February 2005 ; accepted in final form 9 February 2006

IL-6 mediates many aspects of the exercise-induced acute-phase response, including upregulation of antioxidant defenses. Moreover, IL-6 synthesis is regulated in part by oxidative stress. This investigation tested the hypothesis that an IL-6-mediated acute-phase response after exercise provides negative-feedback protection against exercise-induced oxidative stress. Healthy young (n = 16, 26.4 ± 1.8 yr) and older men (n = 16, 71.1 ± 2.0 yr) ran downhill for 45 min at 75% maximal oxygen consumption before and after a 12-wk period of supplementation with vitamin E (1,000 IU/day) or placebo. Circulating IL-6 and soluble IL-6 receptors, peripheral mononuclear cell production of IL-6, and IL-6 transcripts in muscle were measured before and within a 72-h time window after each acute exercise bout. At all time points plasma IL-6, IL-6 bioavailability, and C-reactive protein were higher in the older men; yet in response to exercise, young and older subjects experienced similar increases in these factors. Although the magnitude of postexercise changes in acute-phase variables was independent of age, correlations among plasma, mononuclear cell, and muscle IL-6 and oxidative stress were evident only in young men (R² = 0.64, 0.35, and 0.33, respectively). These changes in circulating IL-6 were closely associated with a prooxidant state (R² = 0.47), whereas muscle IL-6 mRNA correlated with an antioxidant state (R² = 0.65). Supplementation with vitamin E did not affect exercise-induced responses or differences between the young and old men in a consistent manner. Therefore, oxidative stress is linked to the acute-phase response after exercise in young men, but not in older men who had elevated acute-phase reactants, suggesting that further research is warranted to determine the basis for these differences.

interleukin-6; soluble interleukin-6 receptors; glycoprotein 130; F₂-isoprostanes; C-reactive protein; oxygen radical absorbance capacity

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