LEUKEMIA INHIBITORY FACTOR (LIF) INFUSION STIMULATES SKELETAL-MUSCLE REGENERATION AFTER INJURY - INJURED MUSCLE EXPRESSES LIF MESSENGER-RNA

Leukemia inhibitory factor (LIF) is known to stimulate myoblast growth in culture via direct receptor mediated mechanisms, but it does not suppress myoblast fusion in vitro. We show here that LIF is also effective in vivo, using a muscle crush model. Administration of LIF to the site of the crush results in an increased rate of regeneration of the injured muscle. LIF stimulates an increase in the size of the muscle fibers rather than an increase in total number. Perfusion of I-125-labelled LIF (I-125-LIF) at the site of the crush leads to uptake of the great majority of I-125-LIF into the muscle, which suggests that LIF is acting directly at the site of injury. Further, following crush injury LIF mRNA synthesis commences in the muscle. These data provide evidence that LIF is acting as a natural trauma factor in vivo and is actively involved in muscle regeneration.