title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba, 270-0034.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nakamura
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawagoe
authors.forename: Sayaka
authors.initials: S
authors.lastname: Maeda
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016022:Case-Control Studies; D004731:Endotoxins / Q000097:blood; D005260:Female; D024243:HMGB1 Protein / Q000097:blood / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000628:therapy*; D011112:Polymyxin B / Q000008:administration & dosage / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000187:drug effects*; D012772:Shock, Septic / Q000097:blood / Q000628:therapy*
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D024243:HMGB1 Protein; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011112:Polymyxin B