Chaudhry Rajeev, Madden-Fuentes Ramiro J, Ortiz Tara K, Balsara Zarine, Tang Yuping, Nseyo Unwanaobong, Wiener John S, Ross Sherry S, Seed Patrick C
Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina.
J Urol. 2014 May;191(5):1454-61. doi: 10.1016/j.juro.2013.12.013. Epub 2013 Dec 14.
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.
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.
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.
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.
尿路感染在脊髓损伤患者中会导致严重发病。实验性大肠杆菌尿路感染的体内脊髓损伤大鼠模型模拟人类疾病，与对照组相比，对尿路感染的易感性增强。我们假设炎症反应失调会导致对尿路感染的易感性增强。
对脊髓损伤和假手术损伤的大鼠经尿道接种大肠杆菌。在感染前、感染后24小时以及抗生素治疗5天后，测量每组膀胱组织中84个炎症通路基因的转录水平。
感染前，定量聚合酶链反应阵列显示，与对照膀胱相比，脊髓损伤膀胱中促炎因子转录本slc11a1、ccl4和il1β上调超过两倍，抗菌肽lcn2和mpo下调。感染后24小时，与对照组相比，脊髓损伤膀胱的固有免疫反应减弱，il6、slc11a1、il1β和lcn2的表达降低，il10和slpi的表达也降低。尽管抗生素清除了菌尿，但与对照组相比，脊髓损伤大鼠的il6转录诱导延迟，抗炎反应延迟且il10和slpi转录水平降低。
脊髓损伤膀胱对大肠杆菌感染未能产生典型的炎症反应，感染消除后也无法抑制炎症。这可能通过神经介导的途径导致对尿路感染的易感性增加和持续性慢性炎症，据我们所知，这些途径仍有待确定。
