SYSTEMIC ADMINISTRATION OF CILIARY NEUROTROPHIC FACTOR INDUCES CACHEXIA IN RODENTS

Ciliary neurotrophic factor (CNTF) has previously been shown to promot e the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induc e potent effects in extra-neural tissues. Implantation of C6 glioma ce lls engineered to secrete CNTF either subcutaneously or into the perit oneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNF, resulted in a rapid syndrome of weight loss res ulting in death over a period of 7-10 d. This weight loss could not be explained by a reduction in food intake and involved losses of both f at and skeletal muscle. CNTF also induced the synthesis of acute phase proteins such as haptoglobin. Implantation of C6 lines expressing a n onsecreted form of CNTF, or the parental C6 line itself, did not resul t in wasting effects. Analysis of this CNTF-induced wasting indicates similarities with the previously described cachectins, tumor necrosis factor, interleukin 6, and leukemia inhibitory factor, but does not in volve the induction of these cytokines.