Physiological effects of CNTF-induced wasting.
The authors have shown previously that in addition to its survival effects on neurons and glia, ciliary neurotrophic factor (CNTF) induced potent cachectic effects and acute phase proteins when present in the peripheral circulation at concentrations of < or = 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. Mice implanted with C6 glioma cells, genetically modified to secrete CNTF, 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 atrophy, with a disproportionate loss of CD4+/CD8+ T cells. This cachectic 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 members, and the therapeutic use of factors such as CNTF in vivo.
Henderson
J T
JT
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Mullen
B J
BJ
Roder
J C
JC
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016516:CD4-CD8 Ratio; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor; D005260:Female; D005434:Flow Cytometry; D005704:Gallbladder / Q000187:drug effects; D017370:Interleukin-11 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D014280:Triglycerides / Q000097:blood; D014407:Tumor Cells, Cultured; D019282:Wasting Syndrome / Q000139:chemically induced*
D001786:Blood Glucose; D020934:Ciliary Neurotrophic Factor; D017370:Interleukin-11; D015850:Interleukin-6; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D014280:Triglycerides