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

doi:10.1016/j.juro.2013.12.013

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host

J Urol. 2014 May;191(5):1454-61. doi: 10.1016/j.juro.2013.12.013. Epub 2013 Dec 14.

Authors

Rajeev Chaudhry¹, Ramiro J Madden-Fuentes¹, Tara K Ortiz¹, Zarine Balsara¹, Yuping Tang², Unwanaobong Nseyo¹, John S Wiener³, Sherry S Ross³, Patrick C Seed⁴

Affiliations

¹ Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
² Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
³ Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
⁴ 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.

PMID: 24342147
DOI: 10.1016/j.juro.2013.12.013

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.

Keywords: Escherichia coli; cytokines; neurogenic; spinal cord injuries; urinary bladder; urinary tract infections.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cystitis / microbiology*
Escherichia coli Infections / complications*
Female
Rats
Rats, Sprague-Dawley
Spinal Cord Injuries / complications
Urinary Bladder, Neurogenic / complications*
Urinary Bladder, Neurogenic / etiology
Urinary Tract Infections / complications*