title: Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.
abstract: OBJECTIVE
  Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection.
  
  
  METHODS
  Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy.
  
  
  RESULTS
  Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls.
  
  
  CONCLUSIONS
  Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined.
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Chaudhry
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Ramiro J
authors.initials: RJ
authors.lastname: Madden-Fuentes
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Tara K
authors.initials: TK
authors.lastname: Ortiz
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Zarine
authors.initials: Z
authors.lastname: Balsara
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Unwanaobong
authors.initials: U
authors.lastname: Nseyo
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: John S
authors.initials: JS
authors.lastname: Wiener
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Sherry S
authors.initials: SS
authors.lastname: Ross
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina; Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina; Duke University Medical Center, Durham, North Carolina.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Seed
mesh_terms: D000818:Animals; D003556:Cystitis / Q000382:microbiology*; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications; D001750:Urinary Bladder, Neurogenic / Q000150:complications* / Q000209:etiology; D014552:Urinary Tract Infections / Q000150:complications*
keywords: Escherichia coli; cytokines; neurogenic; spinal cord injuries; urinary bladder; urinary tract infections