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Am J Physiol Regul Integr Comp Physiol 291: R1663-R1668, 2006. First published July 13, 2006; doi:10.1152/ajpregu.00053.2006
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INFLAMMATION AND CYTOKINES

Effect of rhIL-6 infusion on GH->IGF-I axis mediators in humans

Dan Nemet,1,2 Alon Eliakim,1,2 Frank Zaldivar,1 and Dan M. Cooper1

1Pediatric Exercise Research Center, School of Medicine, University of California, Irvine, Orange, California; and 2Child Health and Sports Center, Meir General Hospital, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Submitted 20 January 2006 ; accepted in final form 5 July 2006

Exercise leads to simultaneous increases in mediators signaling apparently antagonistic functional responses such as growth factors and inflammatory mediators. The aim of the present study was to demonstrate the physiological effect of IL-6 on circulating components of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Twelve men (ages 26 ± 2 yr) were divided into two groups (n = 6 in each group), receiving either albumin or recombinant human (rh) IL-6 infusion. IL-6 was infused via an antecubital vein, and a contralateral antecubital vein was used for blood sampling. The IL-6 dose was chosen to reach plasma levels of IL-6 characteristic of intense exercise (5 µg/h, for 3 h, resulting in plasma levels of 100 pg/ml). Blood samples for GH, GH binding protein, IGF-I, and IGF binding protein (IGFBP)-1 and -3 were collected at baseline, 30 min, and 1, 2, 3, 4, 5, and 8 h after the beginning of the rhIL-6 infusion. IL-6 levels increased only in the rhIL-6-infused group (P < 0.0005) and returned to baseline after the infusion was stopped. IL-6 infusion led to a significant increase in GH, peaking 1 h after the beginning of infusion (P < 0.001). A decrease in total IGF-I levels was noted only in the rhIL-6-infused group (P < 0.027). An initial decrease in IGFBP-1 levels was noted in both groups during infusion (P < 0.03). Following the initial decrease, there was a significant increase in IGFBP-1 levels only in the IL-6-infused participants, peaking at 2 after the infusion cessation (P < 0.001). IL-6 infusion had no effect on GH binding protein, IGFBP-3, and acid-labile subunit levels. rhIL-6 levels similar to the levels found after strenuous exercise induced a typical exercise-associated GH->IGF-I axis response (increase GH, decreased IGF-I, and elevated IGFBP-1). The results suggest that IL-6 plays a role in the GH->IGF-I response to intense exercise.

exercise; growth factors; inflammatory mediators; cytokines


Address for reprint requests and other correspondence: D. M. Cooper, Professor of Pediatrics–UCI College of Medicine, Clinical Research Center, Bldg. 25, ZOT 4094-03, 101 The City Drive, Orange, CA 92868 (e-mail: dcooper{at}uci.edu)






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