Inflammatory Response to Escherichia coli Urinary Tract Infection in the Neurogenic Bladder of the Spinal Cord Injured Host

Abstract

No AccessJournal of UrologyInvestigative Urology1 May 2014Inflammatory Response to Escherichia coli Urinary Tract Infection in the Neurogenic Bladder of the Spinal Cord Injured Host Rajeev Chaudhry, Ramiro J. Madden-Fuentes, Tara K. Ortiz, Zarine Balsara, Yuping Tang, Unwanaobong Nseyo, John S. Wiener, Sherry S. Ross, and Patrick C. Seed Rajeev ChaudhryRajeev Chaudhry Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina , Ramiro J. Madden-FuentesRamiro J. Madden-Fuentes Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina , Tara K. OrtizTara K. Ortiz Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina , Zarine BalsaraZarine Balsara Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina , Yuping TangYuping Tang Department of Pediatrics, Duke University Medical Center, Durham, North Carolina , Unwanaobong NseyoUnwanaobong Nseyo Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina , John S. WienerJohn S. Wiener Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina Department of Pediatrics, Duke University Medical Center, Durham, North Carolina , Sherry S. RossSherry S. Ross Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina Department of Pediatrics, Duke University Medical Center, Durham, North Carolina , and Patrick C. SeedPatrick C. Seed 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 View All Author Informationhttps://doi.org/10.1016/j.juro.2013.12.013AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: 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. Materials and 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. References 1 : The management of neurogenic bladder and sexual dysfunction after spinal cord injury. Spine (Phila Pa 1976), suppl2001; 26: S129. Google Scholar 2 : Spina bifida and the total care of spinal myelomeningocele. Arch Dis Child1966; 41: 110. Google Scholar 3 : A UK general practice database study of prevalence and mortality of people with neural tube defects. Clin Rehabil2000; 14: 627. 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Google Scholar 30 : Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection. J Immunol2012; 188: 781. Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 191Issue 5May 2014Page: 1454-1461Supplementary Materials Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.Keywordsneurogenicspinal cord injuriesEscherichia coliurinary bladderurinary tract infectionscytokinesMetrics Author Information Rajeev Chaudhry Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina Equal study contribution. More articles by this author Ramiro J. Madden-Fuentes Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina Equal study contribution. More articles by this author Tara K. Ortiz Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina More articles by this author Zarine Balsara Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina More articles by this author Yuping Tang Department of Pediatrics, Duke University Medical Center, Durham, North Carolina More articles by this author Unwanaobong Nseyo Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina More articles by this author John S. Wiener Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina Department of Pediatrics, Duke University Medical Center, Durham, North Carolina Financial interest and/or other relationship with GlaxoSmithKline. More articles by this author Sherry S. Ross Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina Department of Pediatrics, Duke University Medical Center, Durham, North Carolina More articles by this author Patrick C. Seed 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 More articles by this author Expand All Advertisement PDF downloadLoading ...