Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc Min/+ mouse

Interleukin-6 (IL-6) is necessary for cachexia in Apc (Min/+) mice, but the mechanisms inducing this myofiber wasting have not been established. The purpose of this study was to examine gastrocnemius muscle wasting in the Apc (Min/+) mouse and to determine IL-6 regulated mechanisms contributing to muscle loss. Gastrocnemius type IIB mean fiber cross-sectional area (CSA) from Apc (Min/+) mice decreased 32% between 13 and 22 weeks of age. Apc (Min/+) mice lacking IL-6 did not have type IIB fiber atrophy, while overexpression of circulating IL-6 exacerbated the loss of type IIB fiber CSA in Apc (Min/+) mice. Muscle Atrogin-I mRNA expression was induced at least ninefold at 18 and 22 weeks of age compared to 13-week-old mice. Atrogin-I gene expression was also induced by overexpression of circulating IL-6. These data suggest that high circulating IL-6 levels induce type IIB fiber CSA loss in Apc (Min/+) mice, and circulating IL-6 is sufficient to regulate Atrogin-I gene expression in cachectic mice.