PHYSIOLOGICAL-EFFECTS OF CNTF-INDUCED WASTING

The authors have shown previously that in addition to its survival eff ects on neurons and glia, ciliary neurotrophic factor (CNTF) induced p otent cachectic effects and acute phase proteins when present in the p eripheral circulation at concentrations of less than or equal to 10 ng /ml. These effects did not depend upon the induction of other cytokine family members, Described here are the specific physiological effects which systemic administration of CNTF can induce in somatic tissue, M ice implanted with C6 glioma cells, genetically modified to secrete CN TF, exhibited rapid catabolism of adipose tissue and skeletal muscle, depressed steady-state levels of glucose and triglycerides, elevations in red blood cell content, gall bladder hypertrophy and thymic atroph y, with a disproportionate loss of CD4(+)/CD8(+) T cells, This cachect ic wasting resulted in death over a period of 7-10 days, Implantation of the parental C6 line, or C6 cells which express a non-secreted form of CNTF, did not result in overt effects over this time period, These findings have implications both for the biology of CNTF family member s, and the therapeutic use of factors such as CNTF in vivo. (C) 1996 A cademic Press Limited