Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
ASAIO J. 2010 May-Jun;56(3):210-4. doi: 10.1097/MAT.0b013e3181d68fa4.
High-mobility-group box chromosomal protein 1 (HMGB1) has recently been identified as a late mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. It is well known that the cationic portion of HMGB1 binds to heparin, which has abundant sulfates in its structure. In this study, we determined whether spherical sulfated cellulose (SC) efficiently adsorbed HMGB1, as well as other inflammatory mediators, in vitro. Then, we investigated the efficacy of hemoperfusion with the SC (SC group) or cellulose beads (control group) at adsorbing endogenous mediators, including HMGB1, in vivo. We have demonstrated that the SC adsorbed significantly larger amounts of HMGB1, interleukin (IL)-4, and IL-8 when compared with cellulose beads, in vitro. Hemoperfusion with the SC for 30 minute, starting 2 hour after an abdominal opening and closure operation, significantly reduced serum HMGB1 levels (p = 0.004) and consistently increased serum IL-10 levels, in vivo. These data suggest the potential benefits of hemoperfusion using the SC in treating HMGB1-mediated inflammatory diseases.
高迁移率族蛋白 B1（HMGB1）最近被鉴定为各种急性和慢性炎症的晚期介质。从全身循环中有效去除 HMGB1 的方法可能是治疗 HMGB1 介导的炎症性疾病的有前途的方法。众所周知，HMGB1 的阳离子部分与肝素结合，肝素结构中含有丰富的硫酸盐。在这项研究中，我们确定了球形硫酸化纤维素（SC）是否能有效地在体外吸附 HMGB1 以及其他炎症介质。然后，我们研究了 SC（SC 组）或纤维素珠（对照组）在体内吸附内源性介质（包括 HMGB1）的血液灌流的效果。我们已经证明，与纤维素珠相比，SC 在体外吸附了大量的 HMGB1、白细胞介素（IL）-4 和 IL-8。在腹部切开和闭合手术后 2 小时开始进行 30 分钟的 SC 血液灌流，显著降低了血清 HMGB1 水平（p=0.004），并持续增加了血清 IL-10 水平，体内。这些数据表明，使用 SC 进行血液灌流在治疗 HMGB1 介导的炎症性疾病方面具有潜在的益处。
