DEVELOPMENT OF CYTOKINE ADSORPTION COLUMN AND THE TREATMENT OF MULTIPLE ORGAN FAILURE BY CYTOKINE ADSORPTION COLUMN

细胞因子在多器官功能衰竭(MOF)的病理生理学中起重要作用。本研究旨在开发一种选择性地从血流中去除细胞因子的细胞因子吸附柱，并建立一种治疗多器官功能衰竭的新方法。为了开发一种新的细胞因子吸附柱，研究了已在临床上应用于各种疾病的免疫吸附柱或正在开发中的各种吸附剂对细胞因子的吸附性能。在被测试的吸附剂中，Lixelleβ2-用于透析相关淀粉样变性的吸附柱和CF-X(用于自身免疫性疾病的免疫吸附柱)已经被开发。发现它们对各种细胞因子具有很高的亲和力，并选择这些吸附剂开发细胞因子吸附色谱柱。虽然CF-X与肿瘤坏死因子-α的亲和力最高，但它也能吸附正常的γ-球蛋白。为此，研制了一种新型MPC涂层吸附剂(MPC-FX)。MPC-FX可以有效地吸附各种细胞因子，而不吸附正常的Ig G，但由于公司的情况，MPC-FX柱的开发被放弃了。对一种新型的吸附革兰氏阳性菌超抗原的吸附剂T-SAAF进行了试验。体外研究表明，T-SAAF能吸附多种细胞因子。T-SAAF已经在动物模型中进行了安全性和有效性的评估。临床试验将在不久的将来开始。在临床研究中，应用血液IL-6快速检测系统对细胞因子吸附柱的适应证进行了研究。血IL-6水平<10000pg/mL的患者即使使用PMMA-CHDF也难以控制高细胞因子血症，且预后较差。已证实细胞因子相关基因的遗传多态与这些患者的高细胞分裂素血症有关。这些病人。将是应用细胞因子吸附柱的很好的候选者。

Cytokines plays an important role in the pathophysiology of multiple organ failure (MOF). This study was undertaken to develop a cytokine adsorption column, which selectively removes cytokines from blood stream, and to establish a new therapeutic modality for the treatment of MOF. Various adsorbents, which are already clinically applied as immunoadsorption columns for the treatment of various diseases or under development were investigated on their cytokine adsorptive property for development of a new cytokine adsorption column. Among tested adsorbents, Lixelle β2-adsorbing column for dialysis related amyloidosis) and CF-X (developing as an immunoadsorption column for autoimmune diseases) have been. revealed to have high affinity to various cytokines and these adsorbents were selected for the development of a cytokine adsorption column. Although CF-X had the highest affinity to TNF-α, it also adsorbed normal γ-globulin. Therefore, a new MPC coated adsorbent (MPC-FX) was developed. MPC-FX could effectively adsorb various cytokines without adsorbing normal Ig G. However, the development of MPC-FX column abandoned because of circumstances of company. A new adsorbent T-SAAF, which was developed to adsorb super antigen of gram positive bacteria, was tested. T-SAAF has been revealed to adsorb various cytokines in vitro study. T-SAAF has been evaluated its safety and efficacy in animal models. Clinical trials would be started near future. In a clinical study, indication of cytokine adsorption columns was studied with rapid measurement system of blood IL-6. Patients with IL-6 blood levels >10,000pg/mL were difficult to control hypercytokinemia even with PMMA-CHDF and had poor prognosis. It was confirmed that genetic polymorphisms in cytokine related genes were related to hypercytokinemia among these patients. These patients. would be good candidates for the application of a cytokine adsorption column.