The Effects of IL-6 Infusion on the GH???>IGF-I System in Humans

Abstract

1567 Recent investigations have revealed that the early response to exercise leads to a growth-hormone resistant state rather than the expected anabolic activation of the growth hormone—> insulin like growth factor-I (GH—>IGF-I) axis. This phenomenon is believed to be a result of exercise induced stimulation of proinflammatory cytokines [such as interleukin-6 (IL-6)] known to directly inhibit anabolic activity of the GH—>IGF-1 axis. PURPOSE: To test the hypothesis that an IV infusion of IL-6 will induce changes in the GH—> IGF-I axis mediators similar to those observed in acute exercise in humans. METHODS: Twelve young healthy volunteers were randomly assigned to receive a low dose of recombinant human (rh)IL-6 (n = 6) or saline (n = 6) for 3 h. IL-6, GH, IGF-I (total and free), IGFBP-1&3, GHBP and Insulin were measured at baseline, 30 minutes, 1, 2 and 3 hours during the infusion and 1, 2 and 5 hours after the infusion was stopped. Significance level was set at p<0.05. RESULTS: Plasma IL-6 levels during rhIL-6 infusion were 140 pg/ml, corresponding to the levels obtained during very strenuous exercise. No significant effects on body temperature, mean arterial pressure, or heart rate were noted. During the rhIL-6 infusion an increase in GH levels was observed at 1 hour. In addition, a decrease in IGF-I was noted at 3 hours. Two hours post-rhIL-6 infusion an increase in IGFBP-1 was noted, irrespective to changes in insulin. No significant changes were observed for GHBP, IGFBP-3. CONCLUSIONS: These findings supports the hypothesis that physiological concentrations of IL-6, equivalent to those seen following strenuous exercise play a major role in exercise-induced changes in the GH—>IGF-I axis.