Jeffrey T. Henderson,Brendon J.M. Mullen, and John C. Roder

Samuel Lunenfeld Research Institute, Mount SinaiHospital,
Program and Development and Fetal Health, 600University Ave., Toronto, Ontario M5G-1X5

Cytokine, 8(10), pp. 784-793,1996  

Abstract

The authors have shown previouslythat in addition to its survival effects on neurons and glia, ciliary neurotrophicfactor (CNTF) induced potent cachectic effects and acute phase proteinswhen present in the peripheral circulation at concentrations of less thanor equal to 10 ng/ml. These effects did not depend upon the induction ofother cytokine family members. We describe here the specific physiologicaleffect which systemic administration of CNTF can induce in somatic tissues.Mice implanted with C6 glioma cells, genetically modified to secrete CNTF,exhibited rapid catabolism of adipose tissue and skeletal muscle, depressedsteady-state levels of glucose and triglycerides, elevations in red bloodcell content, gall bladder hypertrophy and thymic atrophy, with a disproportionateloss of CD4+/CD8+ T cells. This cachectic wasting resulted in death overa period of 7-10 days. Implantation of the parental C6 line, or C6 cellswhich express a non-secreted form of CNTF, did not result in overt effectsover this time period. These findings have implications both for the biologyof CNTF family members, and the therapeutic use of factors such as CNTF in vivo. 
 

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