title: Filtration leukocytapheresis therapy ameliorates lipopolysaccharide-induced systemic inflammation in a rat model.
abstract: BACKGROUND
  Systemic inflammation, which is associated with various conditions such as sepsis, pneumonia, and trauma, can lead to multiple organ dysfunction syndrome. Systemic inflammation can be life-threatening and is often associated with conditions seen in the intensive care unit. Leukocytes exert a proinflammatory effect and damage various tissues during systemic inflammation. The purpose of this study was to determine whether leukocytapheresis therapy can prevent lipopolysaccharide (LPS)-induced systemic inflammation in a rat model.
  
  
  METHODS
  Male Wistar rats weighing 250 to 300 g were used for all experiments. Rats received an LPS injection, followed 6 h later by filtration leukocytapheresis or mock treatment for 30 min under sevoflurane anesthesia. Systemic inflammation was induced in rats by intravenous LPS injection (7.5 mg/kg) followed by filtration leukocytapheresis. Following blood filtration, we evaluated lung and liver histology, serum cytokine levels, and survival rate of rats for each treatment group.
  
  
  RESULTS
  Histologic examination revealed markedly reduced inflammatory injury in lung and liver tissue harvested from rats 24 h after leukocytapheresis therapy compared with mock treatment. LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion was also inhibited by leukocytapheresis therapy. Moreover, survival was significantly increased in rats treated with high-efficiency leukocytapheresis compared to mock-treated rats (P<0.05).
  
  
  CONCLUSIONS
  Taken as a whole, our findings indicate that filtration leukocytapheresis therapy protects against LPS-induced systemic inflammation. Therefore, leukocytapheresis shows potential as a new therapy for various systemic inflammatory diseases.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan. saku@med.oita-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Akira
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Seigo
authors.initials: S
authors.lastname: Hidaka
authors.forename: Aya
authors.initials: A
authors.lastname: Uno
authors.forename: Kaori
authors.initials: K
authors.lastname: Ueo
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Uchida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000628:therapy; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007937:Leukapheresis / Q000379:methods*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha