CYTOKINES BLOCK THE EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) ON GLUCOSE-UPTAKE AND LACTATE PRODUCTION IN SKELETAL-MUSCLE BUT DO NOT INFLUENCE IGF-I-INDUCED CHANGES IN PROTEIN-TURNOVER

There is evidence that proinflammatory cytokines are involved in the r egulation of muscle protein breakdown in various catabolic conditions but the mechanisms are not fully understood. Previous studies suggest that cytokines reduce circulating and tissue levels of insulin-like gr owth factor-I (IGF-I) and may block the anabolic effects of the hormon e in certain cell types and tissues. We tested the hypothesis that a m ixture of tumor necrosis factor alpha, interleukin-1 alpha, and interf eron-gamma block the anabolic effects of IGF-I in skeletal muscle. Mus cles from burned or unburned rats were incubated in the absence or pre sence of 1 mu g/mL of IGF-I with or without the addition of the cytoki nes. As expected, IGF-I stimulated protein synthesis and inhibited pro tein breakdown in incubated muscles. The cytokines did not influence p rotein turnover rates in muscles incubated with or without IGF-I. In a dditional experiments, the effects of IGF-I on glucose uptake and lact ate production were tested. IGF-I increased glucose uptake similar to 2.5-fold and stimulated lactate production similar to 5-fold. These ef fects of the hormone were significantly inhibited by the cytokine mixt ure. The results suggest that cytokines do not induce protein cataboli sm by directly inhibiting the anabolic effects of IGF-I in muscle tiss ue. The inhibitory effects of the cytokines on IGF-I-stimulated glucos e transport and lactate production suggest that the lack of effect of cytokines on protein metabolism was not due to a metabolic unresponsiv eness of the incubated muscles to the cytokines.