Introduction

While inflammation is an important innate defense mechanism against infection, it can also lead to local tissue damage. The trans signaling pathway of interleukin (IL)-6 is a known mediator of inflammation. We hypothesized that the trans IL-6 signaling pathway is associated with the development of post febrile urinary tract infection (UTI) renal scarring.

Objective

To compare soluble regulators of trans IL-6 signaling between patients with a history of febrile UTI who do or do not have renal scarring.

Study design

After IRB-approval, we collected urine samples in pediatric patients with a history of febrile (≥38 °C) UTI (urine culture >50 K uropathogen) with documented presence or absence of renal scarring on imaging. Samples were collected at a time when patients were not actively infected. Enzyme-linked immunosorbent assays were performed on samples for markers of trans IL-6 signaling: IL-6, soluble (s) IL-6 receptor (R), and soluble (s)gp130, a buffer in trans IL-6 signaling. Values were normalized to urine creatinine. Results were analyzed by t-test or Mann–Whitney U. Spearman rank correlation was used. A p-value of <0.05 was considered significant.

Results

A total of 50 urines from patients with a history of febrile UTI were collected: 23 with and 27 without scarring. There was no difference between groups regarding age or gender. There was no significant difference in urine IL-6, sIL-6R, or sgp130 between those with and without scarring (Figure). While IL-6 values significantly correlated with sIL-6R and sgp130 in those without renal scarring, IL-6 did not correlate with sgp130 in those with scarring. Ratios of IL-6 to sgp130 and sIL-6R to sgp130 were not different between groups.

Discussion

The inflammatory response generated in response to infection is believed to be largely responsible for the development of renal scarring after UTI. IL-6 is a cytokine known to be induced during UTI with a pro-inflammatory pathway, known as trans signaling. This study investigated for differences in markers of trans IL-6 signaling between patients with a history of febrile UTI with and without renal scarring. There was no significant difference between the absolute values or ratio of these markers between groups.

Conclusions

Markers of trans IL-6 signaling are not different between individuals with a history of febrile UTI with and without renal scarring in the non-acute setting.

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Summary Fig. 1. Urine sample results of trans IL-6 signaling markers in patients with a history of febrile UTI who do not have scarring (NS) compared to those with scarring (S).

中文翻译：

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反式 IL-6 信号传导似乎在尿路感染后的肾脏瘢痕形成中没有作用。

介绍

虽然炎症是抵抗感染的重要先天防御机制，但它也可能导致局部组织损伤。白细胞介素 (IL)-6的反式信号通路是已知的炎症介质。我们假设反式IL-6 信号通路与发热后尿路感染 (UTI) 肾瘢痕形成有关。

客观的

比较有或没有肾瘢痕形成的发热性 UTI 病史的患者之间反式IL-6 信号传导的可溶性调节剂。

学习规划

在 IRB 批准后，我们​​收集了有发热 (≥38 °C) UTI（尿培养 > 50 K 尿路病原体）病史的儿科患者的尿样，并在影像学上记录了是否存在肾瘢痕。在患者没有被积极感染的时候收集样本。对样品进行酶联免疫吸附测定以检测反式IL-6 信号转导的标志物：IL-6、可溶性 (s) IL-6 受体 (R) 和可溶性 (s)gp130（反式IL-6 信号转导中的缓冲液）。将值标准化为尿肌酐。通过t检验或 Mann-Whitney U分析结果。使用 Spearman 等级相关。p 值 <0.05 被认为是显着的。

结果

共收集了 50 份来自有发热性 UTI 病史的患者的尿液：23 份有疤痕，27 份没有疤痕。在年龄或性别方面，各组之间没有差异。有瘢痕和无瘢痕的患者的尿液 IL-6、sIL-6R 或 sgp130 没有显着差异（图）。虽然在没有肾瘢痕的患者中，IL-6 值与 sIL-6R 和 sgp130 显着相关，但在有瘢痕的患者中，IL-6 与 sgp130 不相关。IL-6 与 sgp130 和 sIL-6R 与 sgp130 的比率在各组之间没有差异。

讨论

对感染产生的炎症反应被认为是尿路感染后肾脏瘢痕形成的主要原因。IL-6 是一种已知在 UTI 期间通过促炎途径（称为反式信号传导）诱导的细胞因子。本研究调查了有发热性 UTI 病史伴或不伴肾瘢痕形成的患者之间反式IL-6 信号转导标志物的差异。组间这些标志物的绝对值或比率之间没有显着差异。

结论

在非急性环境中，具有和不具有肾瘢痕形成的发热性 UTI 病史的个体之间的反式IL-6 信号传导标志物没有差异。

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总结图1。与有瘢痕形成 (S) 的患者相比，没有瘢痕形成 (NS) 的发热性 UTI 病史患者的反式IL-6 信号标志物的尿液样本结果。