Uno H, Ueki Y, Murashima J, Miyake S, Tominaga Y, Eguchi K, Yano K
Department of Internal Medicine, Sasebo Chuo Hospital, Japan.
Atherosclerosis. 1995 Jul;116(1):93-102. doi: 10.1016/0021-9150(94)05532-n.
There is increasing evidence that immune processes are important in the development of atherosclerosis. We investigated whether low density lipoprotein (LDL) adsorption therapy affected serum cytokine levels and the expression of adhesion molecules on peripheral blood mononuclear cells (lymphocytes and monocytes) in patients with arteriosclerotic obliterance (ASO).
LDL adsorption therapy was repeated ten times over a period of three months in ten ASO patients. The total serum cholesterol and LDL cholesterol levels were significantly reduced at the end of therapy. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured serum levels of inflammatory cytokines (interleukin-1 beta (IL-1 beta), IL-6 and tissue necrosis factor alpha (TNF-alpha)) and expression of adhesion molecules (lymphocyte function-associated antigen 1 alpha (LFA-1 alpha), LFA-1 beta, CD2, very late antigen (VLA)-4, VLA-5 and CD44) on mononuclear cells in the same patients and a group of healthy subjects. Serum levels of all inflammatory cytokines were markedly higher in ASO patients compared with healthy subjects, but there was no significant difference in the level before and after LDL adsorption. VLA-4 expression on CD3+ cells, but not of other adhesion molecules, was markedly higher in ASO patients compared with healthy subjects. LDL adsorption caused a significant reduction in CD2, VLA4 and VLA-5 expression on CD3+ cells. Furthermore, VLA-4 and VLA-5 expression on monocytes diminished significantly after LDL adsorption.
Our results indicate that LDL adsorption-induced immunoregulation is mediated by an indirect stimulatory effect on the immune system. The results suggests that improved peripheral circulation produced by LDL adsorption may reflect improved immune dysfunctions of atherosclerotic lesions in ASO patients.
越来越多的证据表明免疫过程在动脉粥样硬化的发展中起重要作用。我们研究了低密度脂蛋白（LDL）吸附疗法是否会影响动脉硬化闭塞症（ASO）患者的血清细胞因子水平以及外周血单个核细胞（淋巴细胞和单核细胞）上黏附分子的表达。
对10例ASO患者在三个月内重复进行10次LDL吸附治疗。治疗结束时，血清总胆固醇和LDL胆固醇水平显著降低。这与Fontaine分级和踝压指数的显著改善相关。我们还测量了同一组患者以及一组健康受试者血清中炎性细胞因子（白细胞介素-1β（IL-1β）、IL-6和肿瘤坏死因子-α（TNF-α））的水平以及单个核细胞上黏附分子（淋巴细胞功能相关抗原1α（LFA-1α）、LFA-1β、CD2、极迟抗原（VLA）-4、VLA-5和CD44）的表达。与健康受试者相比，ASO患者血清中所有炎性细胞因子水平均显著升高，但LDL吸附前后水平无显著差异。与健康受试者相比，ASO患者CD3⁺细胞上VLA-4的表达显著升高，而其他黏附分子的表达无显著差异。LDL吸附导致CD3⁺细胞上CD2、VLA4和VLA-5的表达显著降低。此外，LDL吸附后单核细胞上VLA-4和VLA-5的表达显著降低。
我们的结果表明，LDL吸附诱导的免疫调节是由对免疫系统的间接刺激作用介导的。结果表明，LDL吸附改善外周循环可能反映了ASO患者动脉粥样硬化病变免疫功能障碍的改善。
