2003 Fiscal Year Final Research Report Summary
DEVELOPMENT OF CYTOKINE ADSORPTION COLUMN AND THE TREATMENT OF MULTIPLE ORGAN FAILURE BY CYTOKINE ADSORPTION COLUMN
| Project/Area Number |
13671216
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
ODA Shigeto CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究院, 助教授 (90204205)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Kenichi CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, LECTURER, 医学部附属病院, 講師 (60282480)
SHIGA Hidetoshi CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, LECTURER, 医学部附属病院, 講師 (20282478)
HIRASAWA Hiroyuki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (80114320)
NAKAMURA Masataka CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, ASSISTANT, 医学部附属病院, 助手 (30315436)
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| Project Period (FY) |
2001 – 2003
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| Keywords | cytokine / selective adsorption / multiple organ failure / MPC-FX / T-SAAF |
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| Research Abstract |
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.
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