Suppression of high-mobility group box-1 and receptor for advanced glycation end-product axis by polymyxin B-immobilized fiber hemoperfusion in septic shock patients.

PURPOSE: Endotoxin plays a role in organ failure in septic shock patients. High-mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) axis is also involved in septic shock. We investigated here the effects of endotoxin removal by polymyxin B-immobilized polystyrene fiber (PMX-F) treatment on circulating levels of HMGB1, soluble RAGE (sRAGE), and interleukin-6 (IL-6) in septic shock patients.

MATERIALS AND METHODS: Fifteen septic shock patients (70.1 ± 8.5 years) and 15 age- and sex-matched healthy volunteers were included in this study. Polymyxin B-immobilized polystyrene fiber treatment was repeated twice, separated by an interval of 24 hours. Blood samples were collected before and immediately after the second PMX-F treatment for determinations of biochemical variables.

RESULTS: Systolic and diastolic blood pressures were significantly lower, and endotoxin, IL-6, HMGB1, and sRAGE levels were higher in septic shock patients compared with healthy volunteers. These parameters were significantly improved by PMX-F treatment. The changes in endotoxin obtained by PMX-F treatment were correlated with those in HMGB1, sRAGE, and IL-6. Multiple stepwise regression analysis revealed that IL-6 was a sole independent correlate of endotoxin.

CONCLUSIONS: Our present study suggests that PMX-F treatment could block the HMGB1-RAGE axis in patients with septic shock via removal of endotoxin-induced inflammatory reactions.