An evaluation of leukaemia inhibitory factor as a potential therapeutic agent in the treatment of muscle disease

The exogenous delivery of growth factors and cytokines is a potential therapeutic strategy to alleviate the degenerative effects of primary inherited myopathies such as Duchenne muscular dystrophy. The mdx mouse diaphragm is a model for examining the progressive degeneration of dystrophic muscle. We have delivered leukaemia inhibitory factor to the mdx diaphragm using slow release alginate gels. Previous studies have reported an improvement in the histology of mdx diaphragms after delivery of leukaemia inhibitory factor in a similar manner, but little attention has been paid to the mechanism by which leukaemia inhibitory factor acts. We have used autoradiography to examine cell proliferation, Evans Blue Dye to examine myofibre damage, and morphometric analysis to examine histology in leukaemia-inhibitory-factor-treated diaphragms and compared them with untreated mdx and normal C57B110/ScSn diaphragms. Autoradiography showed that although myoblast proliferation was significantly increased in leukaemia inhibitory factor-treated mdx diaphragms, leukaemia inhibitory factor did not reduce myofibre damage and no histological improvement was observed. The data presented here, while demonstrating a role for leukaemia inhibitory factor in myoblast proliferation, do not support a strong and consistent benefit of leukaemia inhibitory factor on dystrophic muscle in vivo as a means of alleviating the effects of chronic dystrophic muscle degeneration. (C) 2002 Elsevier Science B.V. All rights reserved.