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

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Abstract

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.

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