2015 Volume 6 Issue 2 Pages 107-114
High Mobility Group Box 1 (HMGB1) is released from various cell types and acts as a pro-inflammatory ligand of Toll-like receptors and receptors for advanced glycation end-products. HMGB1 accelerates inflammation during sepsis, disseminated intravascular coagulation (DIC) and multiple organ failure; this often occurs via HMGB1-mediated crosstalk between inflammatory and coagulant processes. We assumed that HMGB1 metabolism was not predominantly dependent on renal function and, therefore, the degree of HMGB1 regulation in blood was independent of urine outflow. During septic shock, Polymyxin-B direct hemoperfusion (PMX-DHP) ameliorates any harmful effect on hemodynamics by not only endotoxin but also endogenous cannabinoid adsorption, and also improves pulmonary oxygenation by the indirect reduction of cytokines (IL-6, HMGB1, etc.) after the adsorption of activated mononuclear cells. However, whether PMX-DHP also directly adsorbs HMGB1 remains controversial; we therefore investigated this possibility at both the clinical and basic science levels, and found that PMX-DHP had no significant, direct effect on blood HMGB1 levels. In DIC, recombinant thrombomodulin (rTM), a very effective drug for this disease, exerts not only anticoagulant but also anti-inflammatory effects via direct anti-HMGB1 activity. Therefore, a combination of PMX-DHP and rTM for the treatment of DIC is expected to block the vicious cycle of a cytokine storm ending up and consequent multiple organ failure. Such combination therapy is effective in septic shock that is accompanied by DIC and is expected to improve patient survival rates.
