Inflammatory 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, Patrick C. Seed*

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1454-1461
Number of pages8
JournalJournal of Urology
Volume191
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Escherichia coli
  • cytokines
  • neurogenic
  • spinal cord injuries
  • urinary bladder
  • urinary tract infections

ASJC Scopus subject areas

  • Urology

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    Chaudhry, R., Madden-Fuentes, R. J., Ortiz, T. K., Balsara, Z., Tang, Y., Nseyo, U., Wiener, J. S., Ross, S. S., & Seed, P. C. (2014). Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host. Journal of Urology, 191(5), 1454-1461. https://doi.org/10.1016/j.juro.2013.12.013