Drage Lauren K L, Robson Wendy, Mowbray Catherine, Ali Ased, Perry John D, Walton Katherine E, Harding Christopher, Pickard Robert, Hall Judith, Aldridge Phillip D
1Centre for Bacterial Cell Biology, Baddiley-Clark Building, Newcastle University, Newcastle upon Tyne, UK.
2Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4AH UK.
Immun Ageing. 2019 Jul 11;16:16. doi: 10.1186/s12979-019-0156-9. eCollection 2019.
Age is a significant risk factor for recurrent urinary tract (rUTI) infections, but the clinical picture is often confused in older patients who also present with asymptomatic bacteriuria (ASB). Yet, how bacteriuria establishes in such patients and the factors underpinning and/or driving symptomatic UTI episodes are still not understood. To explore this further a pilot study was completed in which 30 male and female community based older patients (mean age 75y) presenting clinically with ASB / rUTIs and 15 control volunteers (72y) were recruited and monitored for up to 6 months. During this period symptomatic UTI episodes were recorded and urines collected for urinary cytokine and uropathogenic (UPEC) analyses.
Eighty-six per cent of patients carried (10 ≥ 10 CFU/ml urine) at some point throughout the study and molecular typing identified 26 different strains in total. Analyses of urine samples for ten different cytokines identified substantial patient variability. However, when examined longitudinally the pro-inflammatory markers, IL-1 and IL-8, and the anti-inflammatory markers, IL-5 and IL-10, were significantly different in the patient urines compared to those of the controls ( < 0.0001). Furthermore, analysing the cytokine data of the rUTI susceptible cohort in relation to carriage, showed the mean IL-10 concentration to be significantly elevated ( = 0.04), in patients displaying numbers ≥10 CFU/ml.
These pilot study data suggest that bacteriuria, characteristic of older rUTI patients, is associated with an immune homeostasis in the urinary tract involving the synthesis and activities of the pro and anti-inflammatory cytokines IL-1, IL-5, IL-8 and IL-10. Data also suggests a role for IL-10 in regulating bacterial persistence.
年龄是复发性尿路感染（rUTI）的一个重要风险因素，但在同时存在无症状菌尿（ASB）的老年患者中，临床情况往往较为复杂。然而，菌尿在这类患者中是如何形成的，以及引发有症状UTI发作的因素仍不清楚。为了进一步探究这一问题，我们完成了一项试点研究，招募了30名临床诊断为ASB/rUTIs的社区老年男性和女性患者（平均年龄75岁）以及15名对照志愿者（72岁），并对他们进行了长达6个月的监测。在此期间，记录有症状的UTI发作情况，并收集尿液进行尿细胞因子和尿路致病性大肠杆菌（UPEC）分析。
在整个研究过程中的某个时间点，86%的患者尿液中携带细菌（≥10⁵CFU/ml尿液），分子分型共鉴定出26种不同的细菌菌株。对十种不同细胞因子的尿液样本分析表明患者之间存在很大差异。然而，纵向检查时，与对照组相比，患者尿液中的促炎标志物IL-1和IL-8以及抗炎标志物IL-5和IL-10有显著差异（P<0.0001）。此外，分析rUTI易感队列的细胞因子数据与细菌携带情况的关系，发现在细菌数量≥10⁵CFU/ml的患者中，平均IL-10浓度显著升高（P=0.04）。
这些试点研究数据表明，老年rUTI患者特有的菌尿与尿路免疫稳态有关，涉及促炎和抗炎细胞因子IL-1、IL-5、IL-8和IL-10的合成与活性。数据还表明IL-10在调节细菌持续性方面发挥作用。
