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Altered Kinetics of Interleukin-6 and Other Inflammatory Mediators During Exercise in Children With Type 1 Diabetes
  1. Jaime S. Rosa, BS*†,
  2. Stacy R. Oliver, MS*,
  3. Masato Mitsuhashi, MD, PhD,
  4. Rebecca L. Flores, MS, RD*,
  5. Andria M. Pontello, MS, RD*,
  6. Frank P. Zaldivar, PhD*,
  7. Pietro R. Galassetti, MD, PhD*†
  1. From the *Department of Pediatrics, Institute for Clinical Translational Science; †Department of Pharmacology, School of Medicine, University of California; and ‡Hitachi Chemical Research Center, Irvine, CA.
  1. This research was supported by National Institutes of Health Grants M01-RR00827-28 and K-23 RR018661-01 and by the Juvenile Diabetes Research Foundation Grant 11-2003-332.
  2. Reprints: Jaime S. Rosa, 1305 Hewitt Hall, 843 Health Science Court, University of California, Irvine, Irvine, CA 92612. E-mail: jsrosa{at}uci.edu.

Abstract

Background Leukocyte mobilization and secretions of cytokines, chemokines, and growth factors in children during exercise are necessary biochemical signals for physiological growth and long-term cardiovascular protection. Because of glycemic instability, altered exercise responses, particularly the proinflammatory cytokine interleukin (IL)-6, may occur in type 1 diabetes mellitus (T1DM) that could influence the onset/progression of diabetic vascular complications. Relatively little is known, however, on most molecular aspects of immunomodulatory adaptation to exercise in diabetic children.

Methods We therefore studied 21 children (age, 13.4 ± 0.3 years; 13 boys/8 girls) with T1DM and 21 age-matched healthy controls during 30 minutes of intense and intermittent cycling exercise. Euglycemia was maintained during and for greater than 90 minutes before exercise; blood samples for IL-6 and other cytokines/chemokines were drawn before, during (every 6 minutes), and after (every 15 minutes) exercise.

Results In T1DM, exercise-induced IL-6 peak occurred earlier and with greater magnitude than that in controls; an exploratory analysis of additional inflammatory mediators displayed a similarly accelerated/exaggerated pattern in T1DM, including the kinetic profiles of tumor necrosis factor α, IL-4, IL-12p70, IL-17, granulocyte-monocyte colony-stimulating factor, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and eotaxin (interferon-inducible protein-10 was the only measured variable essentially indistinguishable between groups).

Conclusion Therefore, during intense and intermittent exercise, significant alterations in the immunologic pattern of inflammatory regulation occurred in children with T1DM as compared with healthy controls. Our findings underscore how the understanding of all the underlying molecular mechanisms is a necessary prerequisite for achieving effective use of exercise and the full manifestation of its health benefits, particularly in understudied populations such as children with T1DM who are at increased risk for cardiovascular complications.

Key Words
  • inflammatory cytokine
  • exercise
  • type 1 diabetes
  • children

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