Møller B, Mogensen S C, Wendelboe P, Bendtzen K, Petersen C M
Department of Clinical Immunology, Skejby Sygehus, University of Aarhus, Denmark.
J Infect Dis. 1991 Apr;163(4):886-9. doi: 10.1093/infdis/163.4.886.
Twenty-four patients, including 12 with meningitis, were admitted with meningeal symptoms and fever. Their serum and spinal fluid tumor necrosis factor-alpha (TNF alpha) levels were determined by ELISA. TNF alpha immunoreactivity was found in spinal fluid of 10 meningitis patients and one nonmeningitis patient, whereas 7 sera, 5 from meningitis patients, contained TNF alpha. Levels were significantly higher in spinal fluids than in serum samples, and the TNF alpha bioactivity of spinal fluids and sera was considerably below predictions based on ELISA measurements. Gel filtration chromatography demonstrated the presence of both polymeric (greater than 200 kDa) and oligomeric (10-40 kDa) TNF alpha in spinal fluid. Significant bioactivity was obtained only from samples containing oligomeric cytokine. In agreement with previous in vitro findings, these results strongly indicate that bioactive TNF alpha oligomers form inactive polymers and monomers, which could contribute to the observed in vivo discrepancies between immunoreactive and bioactive protein. Finally, the data support the concept of local central nervous system production of TNF alpha in meningitis.
24例患者因脑膜刺激症状和发热入院，其中包括12例脑膜炎患者。通过酶联免疫吸附测定法（ELISA）测定了他们血清和脑脊液中的肿瘤坏死因子-α（TNFα）水平。在10例脑膜炎患者和1例非脑膜炎患者的脑脊液中发现了TNFα免疫反应性，而7份血清（5份来自脑膜炎患者）中含有TNFα。脑脊液中的水平显著高于血清样本，并且脑脊液和血清的TNFα生物活性远低于基于ELISA测量的预测值。凝胶过滤色谱法显示脑脊液中存在聚合物（大于200 kDa）和寡聚体（10 - 40 kDa）形式的TNFα。仅从含有寡聚体细胞因子的样本中获得了显著的生物活性。与先前的体外研究结果一致，这些结果强烈表明具有生物活性的TNFα寡聚体形成了无活性的聚合物和单体，这可能导致了体内免疫反应性蛋白和生物活性蛋白之间观察到的差异。最后，这些数据支持了脑膜炎中肿瘤坏死因子-α在局部中枢神经系统产生的概念。
