Tailor-made therapy for patients with septic multiple organ failure using a cytokine adsorbing column based on genetic analysis of cytokine related gene polymorphisms

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This study was conducted to establish a novel tailor-made therapy for prevention of septic multiple organ failure (MOF) with anti-cytokine strategy, such as an cytokine adsorbing column, based on the screening of genetically high risk patients of hypercytokinemia using an genetic analysis of cytokine-related genes. To identify the highly related genetic polymorphisms with hypercytokinemia, various reported genetic polymorphisms were analyzed in patients with hypercytokinemia in relation to their clinical course and outcome. Among genetic polymorphisms tested, TNF α-308G/A, IL-1β-511T/A, IL-1ra VNTR polymorphisms were identified to be highly related with uncontrolled hypercytokinemia and poor outcome. We established the screening system to analyze these polymorphisms using real-time PCR in the laboratory within 4-6 hours. To develop a more effective cytokine modulator than PMMA-CHDF, the phase II clinical trial of a newly developed cytokine adsorbing column, CYT-860, in patients with persistent and severe hypercytokinemia was conducted and has been completed. CYT-860-DHP showed significant reduction in cytokine blood levels and resulted in improvement of P/F ratio. Four of 7 enrolled patients were survived and no adverse effect was observed. Further study is needed for clinical approval of this device. As the realistic approach of more potent cytokine modulation, double PMMA-CHDF, in which 2 series of PMMA-CHDF was simultaneously performed, and PMMA-CHDF using a large sized PMMA dialyzer, in which membrane area is double of conventional hemofilter, were evaluated and their efficacy was confirmed clinically. Therefore, we conducted a prospective study to treat patients with hypercytokinemia based on the genetic analysis of cytokine related genes. This tailor-made therapy for hypercytokinemia based on genetic analysis of cytokine-related gene polymorphism has been approved by institute's ethics committee and now on going in our ICU.