栗山 直英

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 and devices are currently in practical use. We hypothesized that hemofilters composed of porous membranes or cytokine-adsorbing membranes could remove HMGB1 from the blood. We performed experimental hemofiltration in vitro using four types of hemofilters composed of different membranes specifically designed for continuous hemofiltration. The test solution was a 1000-mL substitution fluid containing 100 mu g of HMGB1 and 35 g of bovine serum albumin. Experimental hemofiltration was conducted for 360 min in a closed loop circulation system. Among the four membranes, surface-treated polyacrylonitrile (AN69ST) showed the highest capacity to adsorb HMGB1; it adsorbed nearly 100 mu g of HMGB1 in the initial 60 min and showed a markedly high clearance rate (60.8 +/- 5.0 mL/min) at 15 min. The polymethylmethacrylate membrane had half of the adsorption capacity of the AN69ST membrane. Although the highest sieving coefficient for HMGB1 was obtained with the high cut-off polyarylethersulfone membrane, which correlated with a constant filtrate clearance rate, albumin loss was observed. However, no such removal of both HMGB1 and albumin was observed with the polysulfone membrane and tubing. We conclude that continuous hemofiltration using the AN69ST membrane is a promising approach for HMGB1-related sepsis.