加藤 由布

The high mobility group box 1 protein (HMGB1) is an alarmin that plays an important role in sepsis and has been recognized as a promising target with a wide therapeutic window ; however, no drugs or devices are currently in practical use. Here we demonstrate the removal capacity of HMGB1 using seven internationally available membranes in vitro. High cut-off (HCO) membrane showed lower clearance than the adsorbing-membranes such as PMMA and AN69ST. AN69ST showed the dramatically high adsorption clearance of 60 mL/min in dealing with 100 mL/min of test solution flow. Similar results were obtained in the case of plasma. Moreover, no saturation of HMGB1 on AN69ST was observed. For the treatment of septic shock, we have selected the high-volume, high flow modality using 2.1 m^2 PMMA dialyser, with sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA), for breaking the vicious cycle of mediators. In our study, subjects were enrolled as septic shock patients and most patients were in septic shock without renal failure. We demonstrated the effectiveness for septic shock and amazingly high clearance of HMGB1, IL-6. IL-8 and IL-10. Adsorption is a promising mechanism to remove large-molecular-weight cytokines such as HMGB1 effectively.