Many of the anabolic effects of exercise are mediated through insulin-like growth factor-I (IGF-I), but in adolescents, brief exercise training leads to reductions, rather than the expected increase, in circulating IGF-I. Certain cytokines--interleukin-(IL) 1beta (IL-1beta), IL-6 (IL-6), and tumor necrosis factor-alpha--are increased by exercise in adults and are known to inhibit IGF-I. To test the hypothesis that these cytokines might play a role in the adaptation to exercise, we measured the acute effects of exercise on selected cytokines and growth factors in 17 healthy 8- to 11-y-old children (4 females). Designed to mimic patterns and intensity of exercise found in the real lives of American children, the exercise protocol consisted of a 1.5-h soccer practice (of which about 40 min constituted of vigorous exercise). Pre- and postexercise urine and saliva samples were obtained in all subjects and both blood and urine in nine subjects. The exercise led to significant increases in circulating tumor necrosis factor-alpha (18 +/- 7%, p < 0.05) and IL-6 (125 +/- 35%, p < 0.01) as well as a significant increase in the antiinflammatory cytokine IL-1 receptor antagonist (33 +/- 10%, p < 0.01). Urine levels of IL-6 were also substantially increased by exercise (440 +/- 137%, p < 0.0001). Circulating levels of IGF-I were reduced to a small but significant degree (-6.4 +/- 3.2%, p < 0.05), although IGF-binding protein-1 (known to inhibit IGF-I) was substantially increased (156 +/- 40%, p < 0.001). Cytokines are systemically increased after relatively brief exercise in healthy children. This increase may alter critical anabolic agents such as IGF-I and its binding proteins.

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.