THE ROLE OF LEUKEMIA INHIBITORY FACTOR IN SKELETAL-MUSCLE REGENERATION

Although a number of cytokines have been implicated in tissue regenera tion, it is unknown which ones actually function in vivo. Here, we use mice with a targeted mutation in the leukemia inhibitory factor (LIF) gene to examine the role of LIF in muscle regeneration. Using a muscl e crush model, we show that muscle regeneration in LIF knockout mice i s significantly reduced compared to control littermates. Further, targ eted infusion of LIF in both normal and LIF knockout animals stimulate d muscle regeneration, but the stimulation observed was much greater i n the mutant animals than in controls. In contrast, interleukin-6 and transforming growth factor-a, which also stimulate myoblast proliferat ion in vitro, had no effect on regeneration. These findings demonstrat e directly that LIF is involved in regeneration of injured muscle and points to the use of LIF as a therapeutic agent in the treatment of ne uromuscular disease. (C) 1997 John Wiley & Sons, Inc.