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

Dan Nemet,Alon Eliakim,Dan M Cooper,Frank Zaldivar

doi:10.1152/ajpregu.00053.2006

Abstract

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 microg/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.

Highlights

THERE IS AMPLE EVIDENCE THAT exercise, even in healthy people, leads to simultaneous increases in mediators signaling apparently antagonistic functional responses, such as growth hormone (GH), interleukin-6 (IL-6), and insulin-like growth factor-I (IGF-I)
Increasing evidence supports the recent hypothesis that IL-6 produced by contracting skeletal muscle during exercise may act as a systemic signaling protein
Despite the increase in GH levels, we demonstrated an IL-6 infusion-associated reduction in IGF-I

Summary

Introduction

THERE IS AMPLE EVIDENCE THAT exercise, even in healthy people, leads to simultaneous increases in mediators signaling apparently antagonistic functional responses, such as growth hormone (GH), interleukin-6 (IL-6), and insulin-like growth factor-I (IGF-I). The circulating IGF-I response to acute exercise is complex and has a biphasic nature characterized by a brief, initial increase, followed by a later decrease mainly after heavy and prolonged exercise tasks [25, 33] These interactions are important, because many of the health effects of exercise seem to be influenced, by the fragile balance between inflammatory cytokines and growth factors that are altered by physical activity. We hypothesized that IL-6 infusion would induce changes in the GH3 IGF-I axis, similar to the changes observed following acute strenuous exercise This will provide evidence that IL-6 plays a major mechanistic role in the GH3 IGF-I axis response to exercise. We analyzed serum samples obtained from a recently published human study in which rhIL-6 was infused in healthy, resting subjects [22]

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