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Bladder Injury Activates Innate Immunity During Short-term Foley catheterization in a Swine Model

Abstract: PNFLBA-07
Sources of Funding: Washington University St, Louis Anesthesiology Department_x000D_ World Wide Technology and The Steward Family Foundation

Introduction

Bladder instrumentation by a foreign body (foley catheter) induces inflammation mediated by neutrophil cells. Damage associated molecular patterns (DAMPs); in particular toll-like receptor 9 (TLR9) activate neutrophil production of cytokines. We hypothesized that activation of toll-like receptor 9 (TLR9) induced by necrotic cells may lead to tissue damage.

Methods

After approval by the Animal Care Committee at Washington University in St. Louis, we studied 5 domestic swine receiving a foley catheter. Urine samples were collected over 6 hours. Following cell counts urine neutrophils were labeled with monoclonal antibodies. IL-1?, IL-6, IL-8, IL-10 and TNF-? (figure 1), TLR9, and mitochondrial DNA (mtDNA) (Figure 2), were analyzed by qPCR. Neutrophil Elastase was detected by spectrometry. Specimens from areas of direct contact (urethra, bladder neck and fundus) were stained with H&E (Figure 3). Mann-Whitney U test was performed, p<0.05 was considered significant._x000D_

Results

Foley catheter placement resulted in neutrophilia (p<0.01). Elevated cytokine transcription during the first 3 hours for IL-6, IL-8 (p<0.01), TNF-? (p<0.01), and IL-1? was evident. At 6 hours a noticeable elevation of the anti-inflammatory cytokine IL-10 appeared to reverse proinflammatory cytokine transcription. TLR9 (p<0.001) and mtDNA (p<0.05) transcription was significant. Histology of the bladder at urethra (A), bladder neck (B), and fundus (C) shows diffuse epithelial injury. _x000D_

Conclusions

Cystitis induced by tissue damage is evident by 3 hours of exposure to a foley catheter resulting in elevated neutrophil cytokines, and TLR9 transcription. Therapies to ameliorate early neutrophil activation may prevent inflammation and infection_x000D_

Funding

Washington University St, Louis Anesthesiology Department_x000D_ World Wide Technology and The Steward Family Foundation

Authors
Alexander Earhart
Nicholas Staten
Alana Desai
Henry Lai
Ramakrishna Venkatesh
Carlos Puyo
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