Leukemia inhibitory factor and interleukin-6 are produced by diseased and regenerating skeletal muscle

The process of skeletal muscle regeneration following injury or disease involves locally produced growth factors which control cellular proliferation and differentiation. Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) have previously been shown to promote the proliferation of myoblasts in vitro, and thus may be involved in muscle regeneration. In the present investigation, the in vivo expression of these two myogenic growth factors was examined in regenerating muscle after a crush injury of wild type mice, and in diseased skeletal muscle and diaphragm of the mdxmouse. Using Reverse transcription polymerase chain reaction we have demonstrated that while normal muscle rarely expresses mRNA for these two molecules, there is significant up-regulation following injury, coinciding with the active period of muscle regeneration. This suggests these molecules act as locally produced trauma factors. This observation is reinforced in mdxmouse muscle, which is undergoing a cycle of degeneration and regeneration, and expresses both LIF and IL-6. Using in situ hybridization we have localized mRNA for LIF expression in the mdx diaphragm, suggesting that local production of these molecules by regenerating muscle itself, as well as by other cells in muscle, plays an important role in muscle regeneration.