Journal of Applied Physiology
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J Appl Physiol 100: 1124-1133, 2006. First published December 15, 2005; doi:10.1152/japplphysiol.00562.2005
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Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes

Frank Zaldivar,1 Jessica Wang-Rodriguez,2 Dan Nemet,1,3 Christina Schwindt,1 Pietro Galassetti,1 Paul J. Mills,4 Lori D. Wilson,1 and Dan M. Cooper1

1Pediatric Exercise Research Center, Department of Pediatrics, University Children's Hospital, University of California, Irvine; 2Veterans Affairs San Diego Healthcare System, San Diego; Department of Pathology, University of California, San Diego, California; 3University of Tel Aviv, Meir Hospital, Kfar Saba, Israel; and 4Department of Psychiatry, University of California, San Diego, California

Submitted 12 May 2005 ; accepted in final form 6 December 2005

Leukocytosis following exercise is a well-described phenomenon of stress/inflammatory activation in healthy humans. We hypothesized that, despite this increase in circulating inflammatory cells, exercise would paradoxically induce expression of both pro- and anti-inflammatory cytokines and growth factors within these cells. To test this hypothesis, 11 healthy adult men, 18–30 yr old, performed a 30-min bout of heavy cycling exercise; blood sampling was at baseline, end-exercise, and 60 min into recovery. The percentage of leukocytes positive for intracellular cytokines and growth factors and mean fluorescence intensity was obtained by flow cytometry. Proinflammatory cytokines (IL-1{alpha}, IL-2, IFN-{gamma}, and TNF-{alpha}), a pleiotropic cytokine (IL-6), and anti-inflammatory cytokines and growth factors [IL-4, IL-10, growth hormone (GH), and IGF-I] were examined. Median fluorescence intensity was not affected by exercise; however, we found a number of significant changes (P < 0.05 by mixed linear model and modified t-test) in the numbers of circulating cells positive for particular mediators. The pattern of expression reflected both pro- and anti-inflammatory functions. In T-helper lymphocytes, TNF-{alpha}, but also IL-6, and IL-4 were significantly increased. In monocytes, both IFN-{gamma} and IL-4 increased. B-lymphocytes positive for GH and IGF-I increased significantly. GH-positive granulocytes also significantly increased. Collectively, these observations indicate that exercise primes an array of pro- and anti-inflammatory and growth factor expression within circulating leukocytes, perhaps preparing the organism to effectively respond to a variety of stressors imposed by exercise.

immunology; interleukin-6; growth hormone; intracellular



Address for reprint requests and other correspondence: D. Cooper, Center for the Study of Health Effects of Exercise in Children, Dept. of Pediatrics, Bldg. 25, 2nd Floor, 101 The City Drive, Orange, CA 92868 (e-mail: dcooper{at}uci.edu)




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