UP-REGULATION OF LEUKEMIA INHIBITORY FACTOR AND INTERLEUKIN-6 IN TRANSECTED SCIATIC-NERVE AND MUSCLE FOLLOWING DENERVATION

Leukaemia inhibitory factor (LIF) and Interleukin-6 (IL-6) are multifu nctional cytokines that are related on the basis of their predicted st ructural similarities and shared signal transducing receptor component s. Both these factors stimulate myoblast proliferation, and whereas LI F is neurotrophic for sensory neurons, and for the motor neurons which innervate muscle, IL-6 has only been reported to act on a population of septal neurons in the brain. We have looked at the effect of periph eral nerve trauma on the expression of these factors. We show here tha t whereas LIF and IL-6 mRNAs are expressed in low levels in normal sci atic nerve and skeletal muscle, there is significant up-regulation in the nerve segments after injury, both proximally and distally. There i s also an increase in LIF and IL-6 expression in the denervated muscle located largely in the muscle cells. In addition, while there is retr ograde axonal transport of LIF by the sciatic nerve, IL-6 is not retro gradely transported, and as a result, IL-6 does not stimulate the surv ival of sensory neurons in vitro. Both growth factors are produced by Schwann cells. These results show a rapid response in the expression o f these genes after injury and suggest that LIF and IL-6 act as trauma factors but with different roles in injured peripheral nerve.