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 s uppress myoblast fusion in vitro. We show here that LIF is also effect ive 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 f ibers rather than an increase in total number. Perfusion of I-125-labe lled LIF (I-125-LIF) at the site of the crush leads to uptake of the g reat majority of I-125-LIF into the muscle, which suggests that LIF is acting directly at the site of injury. Further, following crush injur y LIF mRNA synthesis commences in the muscle. These data provide evide nce that LIF is acting as a natural trauma factor in vivo and is activ ely involved in muscle regeneration.