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

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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.