Jurewicz A M, Walczak A K, Selmaj K W
Department of Neurology, Medical University of Lodz, Poland.
Neurology. 1999 Oct 22;53(7):1409-14. doi: 10.1212/wnl.53.7.1409.
To evaluate the rate of shedding of tumor necrosis factor (TNF) receptors (TNFRs) in MS patients.
It was previously suggested that TNF might play a significant role in the immunopathologic mechanism of MS. TNF mediates its biologic effects by interacting with two distinct receptors: TNFR-p55 and TNFR-p75. Both of these receptors exist in soluble and membrane-bound forms. Soluble receptors have been shown to influence TNF activity in vitro and in vivo and maintain balance between active, free TNF and inactive form of this cytokine bound to its soluble receptors.
In the current study, the authors measured shedding of TNFRs from cell surface of peripheral blood mononuclear cells, peripheral blood lymphocytes, and monocytes in three groups of MS patients: relapsing-remitting in relapse, relapsing-remitting in remission, and chronic progressive.
The authors observed a significant distortion in generation of both soluble TNF receptors. Whereas the TNFR-p55 was shed at lower rate compared with healthy volunteers, the shedding of TNFR-p75 was significantly higher in MS patients.
Disturbance in TNFR shedding might contribute to the distortion of a fine balance between circulating TNF and its natural inhibitors in MS.
评估多发性硬化症（MS）患者肿瘤坏死因子（TNF）受体（TNFRs）的脱落率。
此前有研究表明，TNF可能在MS的免疫病理机制中发挥重要作用。TNF通过与两种不同的受体相互作用来介导其生物学效应：TNFR-p55和TNFR-p75。这两种受体均以可溶性和膜结合形式存在。可溶性受体已被证明在体外和体内均可影响TNF活性，并维持活性、游离TNF与其结合在可溶性受体上的无活性形式之间的平衡。
在本研究中，作者测量了三组MS患者外周血单核细胞、外周血淋巴细胞和单核细胞表面TNFRs的脱落情况，这三组患者分别为复发缓解型处于复发期、复发缓解型处于缓解期以及慢性进展型。
作者观察到两种可溶性TNF受体的生成均存在显著异常。与健康志愿者相比，TNFR-p55的脱落率较低，而MS患者中TNFR-p75的脱落率显著更高。
TNFR脱落的紊乱可能导致MS患者循环TNF与其天然抑制剂之间的微妙平衡失调。
