Muscle Wasting and the Role of IL-6 in Cachectic ApcMin/+ Mice

Abstract

Cancer cachexia is characterized by skeletal muscle and adipose tissue mass loss, anemia, and chronic inflammation. Although regulation of cachexia is not well understood, the cytokine interleukin-6 (IL-6) is an excellent candidate for inducing skeletal muscle wasting. Our laboratory has published that the ApcMin/+ mouse, which develops intestinal tumors, undergoes cachexia. This mouse also has elevated levels of circulating IL-6. PURPOSE: The purpose of this study was to determine the role of IL-6 during ApcMin/+ mouse skeletal muscle wasting. METHODS: ApcMin/+ mice were crossed with IL-6 null mice, creating ApcMin/+ × IL-6−/− mice. This cross produced mice that had a similar tumor burden compared to ApcMin/+ mice. Wild-type (n=5), ApcMin/+ (n=7), and ApcMin/+ × IL-6−/- (n=7) mice were compared at 6 months of age. Skeletal muscle weights and gastrocnemius fiber cross-sectional area was analyzed. RESULTS: ApcMin/+ gastrocnemius muscle wet weight (93 ±11 mg) decreased 26% compared to wild-type (126 ± 3 mg) mice. ApcMin/+ × IL-6−/−(125 ± 5 mg) gastrocnemius muscle weight was not different from wild-type mice. Gastrocnemius mean fiber cross-sectional area also decreased in ApcMin/+ mice (1031 ± 122 μm2) compared to wild-type mice (1456 ±115 μm2), but this decrement was not seen in ApcMin/+ × IL-6−/- mice (1529 ± 152 μm2). CONCLUSIONS It appears that inflammatory cytokine IL-6 is necessary for the induction of muscle wasting in the ApcMin/+ mouse.