Leukemia inhibitory factor ameliorates muscle fiber degeneration in the mdx mouse

Although the muscles of the mdx mouse lack dystrophin, the protein absent i n muscles of humans affected with Duchenne muscular dystrophy (DMD), the on ly mdx muscle to degenerate in a manner similar to those of DMD boys is the diaphragm. We have previously shown that leukemia inhibitory factor (LIF) is a trauma factor that enhances muscle repair in vivo and, when applied ex ogenously, increases the fiber size of mdx skeletal muscle. Furthermore, we developed a controlled release device for LIF based on a calcium alginate rod (release rate about 0.5% per day). These rods were sutured to the abdom inal surface of the hemidiaphragm of mdx mice 3 months old. At age 6 months the mice were killed and the diaphragm muscles fixed and sectioned, The se ctions showed obvious muscle degeneration at 3 months of age in mdx mouse d iaphragms and further degeneration at 6 months in saline-perfused muscle. H emidiaphragm muscles continuously exposed to LIF over the same period conta ined more normal myofibers, larger regenerated fibers, and less adipose tis sue and other non-contractile tissue. Morphometric analysis of the diaphrag m sections was carried out. The LIF-treated animals showed a significant in crease in fiber number and size compared to saline rod controls. The amount of nonmuscle (connective tissue and adipose tissue) was significantly redu ced and the maximum force-producing capacity of isolated diaphragm muscle s trips was higher in LIF-treated mice. The results demonstrate that LIF trea tment ameliorates the dystrophic abnormalities in mdx mouse diaphragm. (C) 2000 John Wiley & Sons, Inc.