Rothstein J L, Schreiber H
Division of Biological Sciences, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1988 Jan;85(2):607-11. doi: 10.1073/pnas.85.2.607.
We find a strong synergism between tumor necrosis factor (TNF) and bacteria or their products. Endotoxin-"free" recombinant TNF, even at very high doses (160 micrograms), did not alone cause hemorrhagic necrosis (HN) in the skin of normal mice. Similarly, TNF alone had a low systemic toxicity in tumor- and pathogen-free mice. However, TNF given intravenously with nanogram quantities of the endotoxin lipopolysaccharide caused lethal shock. Furthermore, subcutaneous injection of lipopolysaccharide made skin susceptible to subsequent induction of HN by TNF injected in the same site 24 hr later. Mycoplasma-infected cells or corynebacteria also synergized with TNF to cause HN or lethal shock. In addition, we find that lymphotoxin, a cytokine functionally and genetically related to TNF, also synergized with the bacteria to cause HN, whereas interleukin 1 alpha or interferon gamma did not. Together, the results indicate that a synergy between TNF and bacteria or their products causes HN and lethal shock in normal mice.
我们发现肿瘤坏死因子（TNF）与细菌或其产物之间存在强烈的协同作用。无内毒素的重组TNF，即使剂量非常高（160微克），单独使用时也不会在正常小鼠皮肤中引起出血性坏死（HN）。同样，单独的TNF在无肿瘤和无病原体的小鼠中全身毒性较低。然而，静脉注射纳克量的内毒素脂多糖与TNF一起会导致致死性休克。此外，皮下注射脂多糖会使皮肤在24小时后对同一部位注射的TNF随后诱导的HN敏感。支原体感染的细胞或棒状杆菌也与TNF协同作用，导致HN或致死性休克。此外，我们发现淋巴毒素，一种在功能和基因上与TNF相关的细胞因子，也与细菌协同作用导致HN，而白细胞介素1α或干扰素γ则不会。总之，结果表明TNF与细菌或其产物之间的协同作用会在正常小鼠中导致HN和致死性休克。
