Selmaj K W, Raine C S
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, New York, NY 10461.
Ann Neurol. 1988 Apr;23(4):339-46. doi: 10.1002/ana.410230405.
Recombinant human tumor necrosis factor (rhTNF) has been tested for its effect on myelinated cultures of mouse spinal cord tissue. As controls, recombinant human interferon gamma (rhIFN) and interleukin-2 (rhIL-2) were tested, as well as T-cell supernatants, antigalactocerebroside serum, and normal culture medium. It was found that rhTNF induced delayed-onset (18-24 hr) oligodendrocyte necrosis and a type of myelin dilatation peculiar to this system. Some nerve fibers progressed to demyelination by 72 hours. The myelin dilatation was not reversible by return to normal feeding solution for 3 days. In contrast, rhIFN, rhIL-2, T-cell supernatants, and normal medium had little or no effect on cultures. This mechanism differs from other immune-mediated mechanisms in that it appears that a physiological (not structural) demyelination occurs initially without overt destruction of the myelin sheath. These observations are relevant to the evolution of the multiple sclerosis plaque: dysfunction of ionic channels might contribute to the eventual demise of oligodendrocytes and axons in the longstanding lesion.
重组人肿瘤坏死因子（rhTNF）已被测试其对小鼠脊髓组织有髓培养物的作用。作为对照，测试了重组人干扰素γ（rhIFN）、白细胞介素-2（rhIL-2），以及T细胞上清液、抗半乳糖脑苷脂血清和正常培养基。发现rhTNF诱导迟发性（18 - 24小时）少突胶质细胞坏死以及该系统特有的一种髓鞘扩张。到72小时时，一些神经纤维进展为脱髓鞘。将培养物恢复到正常培养液3天，髓鞘扩张并不能逆转。相比之下，rhIFN、rhIL-2、T细胞上清液和正常培养基对培养物几乎没有影响。这种机制与其他免疫介导机制不同，因为最初似乎发生的是生理性（而非结构性）脱髓鞘，而髓鞘并未受到明显破坏。这些观察结果与多发性硬化斑块的演变相关：离子通道功能障碍可能导致长期病变中少突胶质细胞和轴突最终死亡。
