title: Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells: roles of interleukin-10 and the extracorporeal circuit.
abstract: OBJECTIVE
  To determine whether cardiopulmonary bypass (CPB) alters the ex vivo cytokine production of whole blood cells stimulated by lipopolysaccharide (LPS) and to assess the roles of interleukin (IL)-10 and an extracorporeal circuit (ECC) in the alteration.
  
  
  METHODS
  Prospective, controlled study.
  
  
  METHODS
  Biochemistry laboratory and surgical intensive care unit in a university hospital.
  
  
  METHODS
  Seventeen consecutive adult patients undergoing coronary artery bypass grafting or valve surgery with normothermic CPB and eight healthy volunteers.
  
  
  METHODS
  Blood samples for cytokine measurement were drawn from patients before and during (at 60, 90, 120, 180 and 360 mins) CPB and were cultured with and without LPS and with and without anti-IL-10 antibodies. Blood was also drawn from healthy subjects and sampled for cytokine analysis before and during circulation in an isolated ECC.
  
  
  RESULTS
  The concentrations of ex vivo tumor necrosis factor (TNF)-alpha, IL-6, IL-8, and IL-10, measured by enzyme-linked immunosorbent assay, were reduced in both experimental settings. In patients on CPB, LPS hyporesponsiveness was detected at 60 mins after the onset of CPB and was maximal at 120 mins (78% to 86% decreases from pre-CPB levels) but was transient, except for TNF-alpha. The plasma concentration of IL-10 peaked at 90 mins after the start of CPB, but the role of IL-10 in LPS hyporesponsiveness appears limited because anti-IL-10 antibodies significantly increased ex vivo production of IL-6 but not TNF-alpha or IL-8. In the isolated ECC study, no IL-10 was detected in plasma, yet the ex vivo production of the cytokines (except IL-8) was decreased (by 66% to 95%).
  
  
  CONCLUSIONS
  Our results demonstrate the following: a) CPB induces an early and transient LPS hyporesponsiveness of whole blood as measured by cytokine production; b) IL-10 seems only partly involved in this process, and its role is restricted to an in vivo situation; and c) contact of blood with an ECC is sufficient to induce LPS hyporesponsiveness.
authors.affiliation: Laboratory of Bioch A, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: M S
authors.initials: MS
authors.lastname: Dehoux
authors.forename: S
authors.initials: S
authors.lastname: Hernot
authors.forename: K
authors.initials: K
authors.lastname: Asehnoune
authors.forename: A
authors.initials: A
authors.lastname: Boutten
authors.forename: S
authors.initials: S
authors.lastname: Paquin
authors.forename: V
authors.initials: V
authors.lastname: Leçon-Malas
authors.forename: M L
authors.initials: ML
authors.lastname: Toueg
authors.forename: J M
authors.initials: JM
authors.lastname: Desmonts
authors.forename: G
authors.initials: G
authors.lastname: Durand
authors.forename: I
authors.initials: I
authors.lastname: Philip
mesh_terms: D001773:Blood Cells / Q000378:metabolism*; D002315:Cardiopulmonary Bypass; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016753:Interleukin-10