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

细胞因子吸附柱的研制及细胞因子吸附柱治疗多器官功能衰竭

• 批准号: 13671216
• 负责人: ODA Shigeto
• 金额: $ 2.3万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671216/
• 关键词: cytokine; selective adsorption; multiple organ failure; MPC-FX; T-SAAF; 敗血症性ショック; 全身性炎症反応症候群; 選択的吸着剤; 免疫吸着

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.

细胞因子在多器官功能衰竭（MOF）的病理生理中起重要作用。本研究旨在建立细胞因子吸附柱，选择性地去除血液中的细胞因子，为MOF的治疗建立一种新的治疗方式。对临床已应用于多种疾病的免疫吸附柱或正在开发的各种吸附剂进行细胞因子吸附性能的研究，以开发一种新的细胞因子吸附柱。在已测试的吸附剂中，Lixelle β2吸附柱（用于透析相关淀粉样变性）和CF-X（发展为用于自身免疫性疾病的免疫吸附柱）已被证实。发现对多种细胞因子具有高亲和力，并选择这些吸附剂用于细胞因子吸附柱的开发。虽然CF-X对TNF-α具有最高的亲和力，但它也吸附正常的γ-球蛋白。为此，研制了一种新型的MPC包覆吸附剂（MPC- fx）。MPC-FX可以有效吸附多种细胞因子，而不吸附正常的Ig。但由于公司的情况，MPC-FX色谱柱的开发被放弃。研制了一种吸附革兰氏阳性菌超抗原的新型吸附剂T-SAAF。体外实验显示T-SAAF对多种细胞因子具有吸附作用。T-SAAF已在动物模型上进行了安全性和有效性评价。临床试验将在不久的将来开始。在临床研究中，应用白细胞介素-6快速测定系统研究细胞因子吸附柱的适应症。IL-6水平在10万pg/mL以上的患者即使使用PMMA-CHDF也难以控制高细胞素血症，预后较差。证实细胞因子相关基因的遗传多态性与这些患者的高细胞因子血症有关。这些病人。将是细胞因子吸附柱应用的良好候选者。

项目成果

織田成人 他: "腹部救急疾患に合併した敗血症性ショックに対する治療戦略"日本腹部救急医学会雑誌. 22・5. 791-799 (2002)

Shigeto Oda 等：“感染性休克并发腹部急症的治疗策略”日本腹部急症医学会杂志 22・5（2002 年）。

織田成人, 平澤博之, 志賀英敏, 松田兼一, 上野博一, 仲村将高, 渡遅栄三: "重症感染症の病態とメディエーター"日本外科学会雑誌. 104. 511-517 (2003)

Shigeto Oda、Hiroyuki Hirasawa、Hidetoshi Shiga、Kenichi Matsuda、Hirokazu Ueno、Masataka Nakamura、Eizo Watanabe：“严重感染性疾病的病理学和介质”日本外科学会杂志 104. 511-517 (2003)。

Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamura M: "Therapeutic strategy for patients with septic shock complicated abdominal emergency"Journal of Abdominal Emergency Medicine. 22. 791-799 (2002)

Oda S、Hirasawa H、Shiga H、Nakanishi K、Matsuda K、Nakamura M：“脓毒性休克并发腹部急症患者的治疗策略”腹部急诊医学杂志。

Kenichi Matsuda, et al.: "Current topics in cytokine removal technologies"Therapeutic Apheresis. 5・4. 306-314 (2001)

Kenichi Matsuda 等人：“细胞因子去除技术的当前主题”治疗性血浆分离术 5・4（2001）。

Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamura M: "Continuous hemofilitration/hemodiafiltration in critical care"Therapeutic Apheresis. 6. 193-198 (2002)

Oda S、Hirasawa H、Shiga H、Nakanishi K、Matsuda K、Nakamura M：“重症监护中的连续血液滤过/血液透析滤过”治疗性血浆分离术。