Jeffrey T. Henderson*, Nadine A.Seniuk*, Peter M. Richardson`, Jack Gauldie! and John C. Roder*

* Samuel Lunenfeld Research Institute, Mount SinaiHospital,
   Program in Development and FetalHealth, 600 University Ave., Toronto, Ontario M5G-1X5
`  Department of Neurosurgery, MontrealGeneral Hospital, Montreal, Quebec H3G-1A4
!  Department of Pathology, McMaster University,Hamilton, Ontario L8N-3Z5

Journal of Clinical Investigation,93, pp. 2632-2638, 1994

Abstract

Ciliary neurotrophic factor (CNTF)has previously been shown to promote the survival of several classes ofneurons and glia. We report here that in addition to its effects on thenervous system, CNTF can induce potent effects in extra-neural tissues.Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneouslyor into the peritoneal cavity of adult mice, or systemic injections ofpurified rat or human recombinant CNTF, resulted in a rapid syndrome ofweight loss resulting in death over a period of 7-10 days. This weightloss could not be explained by a reduction in food intake and involvedlosses of both fat and skeletal muscle. CNTF also induced the synthesisof acute phase proteins such as haptoglobin. Implantation of C6 lines expressingan non-secreted form of CNTF, or the parental C6 line itself, did not resultin wasting effects. Analysis of the CNTF-induced wasting indicates similaritieswith the previously described cachectins, tumor necrosis factor, interleukin6, and leukemia inhibitory factor; but does not involve the induction ofthese cytokines.
 

Full Paper