title: Inflammatory status in sepsis alters efficacy of interleukin-18 binding protein therapy.
abstract: OBJECTIVE
  Sepsis remains a serious clinical problem, and multiple attempts at blocking inflammation have failed to decrease mortality rate. Interleukin-18 has been demonstrated to be an important component of the innate immune response to bacterial infections.
  
  
  METHODS
  Previous work demonstrated that elevated plasma concentrations of interleukin-6 obtained in the first 6 hrs of sepsis predict a worse outcome. Mice were subjected to cecal ligation and puncture and, on the basis of the plasma concentration of interleukin-6, were randomized to receive either interleukin-18 binding protein or vehicle approximately 8 hrs after the onset of sepsis.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Adult, female BALB/c mice.
  
  
  METHODS
  We sought to determine the role of interleukin-18 in sepsis by blocking its biological activity with the interleukin-18 binding protein in the murine model of sepsis induced by cecal ligation and puncture.
  
  
  RESULTS
  In this study, elevated plasma concentrations of interleukin-6 were associated with a worse outcome. Treatment with interleukin-18 binding protein decreased inflammation as determined by lower concentrations of plasma interleukin-6 obtained 48 hrs after the onset of sepsis. In mice with increased risk of dying, interleukin-18 binding protein slightly decreased mortality rate. However, in those mice with a predicted low mortality rate, interleukin-18 binding protein significantly increased mortality rate.
  
  
  CONCLUSIONS
  In this study, mice at low risk of death due to sepsis had decreased survival when treated with interleukin-18 binding protein. These results have potential implications for the use of interleukin-18 binding protein for treatment of chronic inflammatory conditions since it may place the host at increased risk of infectious complications.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, 48109-0602, USA. remickd@umich.edu
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Bolgos
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood*; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C118370:interleukin-18 binding protein