title: Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study.
abstract: BACKGROUND
  Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We designed an extracorporeal hemoadsorption device capable of capturing both cytokines and leukocytes in order to test the hypothesis that leukocyte capture would alter circulating cytokine profiles and influence immunological cell-cell interactions in whole blood taken from patients with sepsis.
  
  
  METHODS
  We performed a series of ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood circulated for four hours in closed loops with four specially designed miniaturized extracorporeal blood purification devices including two different hemoadsorption devices and a hemofilter in order to characterize leukocyte capture and to assess the effects of leukocyte removal on inflammation and immune function.
  
  
  RESULTS
  Hemoadsorption was selective for removal of activated neutrophils and monocytes. Capture of these cells led to local release of certain cytokines, especially IL-8, and resulted in complex cell-cell interactions involved in cell-mediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function.
  
  
  CONCLUSIONS
  Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity. Further studies are needed to understand better these cellular interactions in order to help design better blood purification therapies.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rimmelé
authors.forename: Ata Murat
authors.initials: AM
authors.lastname: Kaynar
authors.forename: Joseph N
authors.initials: JN
authors.lastname: McLaughlin
authors.forename: Jeffery V
authors.initials: JV
authors.lastname: Bishop
authors.forename: Morgan V
authors.initials: MV
authors.lastname: Fedorchak
authors.forename: Anan
authors.initials: A
authors.lastname: Chuasuwan
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Peng
authors.forename: Kai
authors.initials: K
authors.lastname: Singbartl
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Frederick
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Melinda
authors.initials: M
authors.lastname: Carter
authors.forename: William J
authors.initials: WJ
authors.lastname: Federspiel
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D000327:Adsorption / Q000502:physiology; D005112:Extracorporeal Circulation / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007962:Leukocytes / Q000276:immunology*; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000628:therapy*