Henderson J T, Mullen B J, Roder J C
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Cytokine. 1996 Oct;8(10):784-93. doi: 10.1006/cyto.1996.0104.
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.
作者先前已经表明，睫状神经营养因子（CNTF）除了对神经元和神经胶质细胞具有存活作用外，当它以≤10 ng/ml的浓度存在于外周循环中时，还会诱导强烈的恶病质效应和急性期蛋白。这些效应并不依赖于其他细胞因子家族成员的诱导。本文描述了全身性给予CNTF可在体细胞组织中诱导的特定生理效应。植入经基因改造以分泌CNTF的C6胶质瘤细胞的小鼠，表现出脂肪组织和骨骼肌的快速分解代谢、葡萄糖和甘油三酯稳态水平降低、红细胞含量升高、胆囊肥大和胸腺萎缩，CD4+/CD8+ T细胞不成比例地减少。这种恶病质消耗在7至10天内导致死亡。植入亲代C6细胞系或表达非分泌形式CNTF的C6细胞，在此时间段内未产生明显影响。这些发现对CNTF家族成员的生物学特性以及CNTF等因子在体内的治疗应用均具有启示意义。
