Berg M, Fraker D L, Alexander H R
Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Cytokine. 1994 Jul;6(4):425-32. doi: 10.1016/1043-4666(94)90067-1.
Alterations in lipid metabolism characterized in major part by a decrease in lipoprotein lipase (LPL) activity in adipose tissue are a central feature of cachexia from chronic infection or malignancy. These metabolic derangements may be mediated in large part through endogenous host proteins produced in response to various pathological stimuli. Differentiation factor/leukaemia inhibitory factor (D-factor) is a cytokine whose functions overlap those of tumour necrosis factor-alpha (TNF), IL-6 and IL-1. Recombinant murine D-factor produced a dose- and time-dependent inhibition of heparin-releasable LPL activity in differentiated 3T3-L1 adipocytes. Although 2-10 fold less potent than recombinant murine TNF, D-factor inhibited LPL activity at concentrations of 1-10 ng/ml. When added together, D-factor and TNF produced a synergistic inhibition of LPL activity. Interleukin 6 (IL-6) was 100-fold less potent than D-factor; 0.1 ng/ml of D-factor or 10 ng/ml of IL-6 caused a 50% inhibition of LPL activity. D-factor and TNF increased IL-6 production in 3T3-L1 cells. Ten ng/ml of D-factor or 1.0 ng/ml of TNF stimulated the release of < 1 ng/ml of IL-6 and inhibited LPL activity to 11 +/- 3% and 3 +/- 2% of control, respectively, whereas 50 ng/ml of recombinant IL-6 was required to decrease LPL activity to 24 +/- 19% of control. TNF produced a marked decrease in LPL mRNA, whereas D-factor had minimal or no effect at doses which inhibited LPL activity almost completely. Western blot analysis of cell extracts showed that TNF caused a greater decrease in LPL protein production than D-factor.2+ with TNF, may contribute to the manifestations of cachexia.
脂质代谢改变主要表现为脂肪组织中脂蛋白脂肪酶（LPL）活性降低，是慢性感染或恶性肿瘤所致恶病质的核心特征。这些代谢紊乱可能在很大程度上是由宿主响应各种病理刺激产生的内源性蛋白质介导的。分化因子/白血病抑制因子（D因子）是一种细胞因子，其功能与肿瘤坏死因子-α（TNF）、IL-6和IL-1的功能重叠。重组小鼠D因子在分化的3T3-L1脂肪细胞中对肝素可释放的LPL活性产生剂量和时间依赖性抑制。尽管其效力比重组小鼠TNF低2至10倍，但D因子在1至10 ng/ml的浓度下可抑制LPL活性。当D因子和TNF一起添加时，会对LPL活性产生协同抑制作用。白细胞介素6（IL-6）的效力比D因子低100倍；0.1 ng/ml的D因子或10 ng/ml的IL-6可导致LPL活性受到50%的抑制。D因子和TNF可增加3T3-L1细胞中IL-6的产生。10 ng/ml的D因子或1.0 ng/ml的TNF刺激释放的IL-6<1 ng/ml，并分别将LPL活性抑制至对照的11±3%和3±2%，而需要50 ng/ml的重组IL-6才能将LPL活性降低至对照的24±19%。TNF使LPL mRNA显著减少，而D因子在几乎完全抑制LPL活性的剂量下影响极小或无影响。细胞提取物的蛋白质印迹分析表明，TNF导致LPL蛋白产生的减少比D因子更显著。与TNF一起，可能导致恶病质的表现。
