Recent studies demonstrate an unexpected reduction in circulating levels of IGF-I after 5 wk of endurance-type exercise training in adolescent boys and girls and prepubertal girls. We hypothesized that the reduction in IGF-I would be accompanied by a training-associated stimulation of proinflammatory cytokines IL-1beta, IL-6, or tumor necrosis factor-alpha (TNF-alpha), each of which can inhibit the GH-->IGF-I axis. Healthy boys (age range 9-11 y old, mean Tanner 1.7) volunteered for the study and were randomized to control (n = 14) and training groups (n = 12) for 5 wk. After the intervention, significant increase in fitness was observed in the training group but not control group. Although IGF-I was correlated at baseline to peak oxygen consumption in all subjects, there was a significant decrease in IGF-I and IGF binding protein-3 in the training subjects (-12.8 +/- 7.3% and -17.5 +/- 7%, respectively, p < 0.05). In contrast, IGF binding protein-2, known to inhibit anabolic effects of IGF-I, increased in the training subjects (27.8 +/- 11%, p < 0.02) as did IL-1beta and TNF-alpha (51.5 +/- 30.22%, p < 0.02, and 44.5 +/- 23.2%, p < 0.02, respectively). Finally, we also found that GHBP was inversely correlated with fitness, suggesting altered GH function in more-sedentary boys. Thus, these data support the hypothesis that a sustained increase in physical activity can stimulate proinflammatory cytokines, which may contribute to suppression of the GH-->IGF-I axis. Physical activity can influence growth and development through its influence on anabolic and catabolic mediators.