Elevated CXC chemokines in urine noninvasively discriminate OAB from UTI

Abstract

Overlapping symptoms of overactive bladder (OAB) and urinary tract infection (UTI) often complicate the diagnosis and contribute to overprescription of antibiotics. Inflammatory response is a shared characteristic of both UTI and OAB and here we hypothesized that molecular differences in inflammatory response seen in urine can help discriminate OAB from UTI. Subjects in the age range of (20-88 yr) of either sex were recruited for this urine analysis study. Urine specimens were available from 62 UTI patients with positive dipstick test before antibiotic treatment. Six of these patients also provided urine after completion of antibiotic treatment. Subjects in cohorts of OAB (n = 59) and asymptomatic controls (n = 26) were negative for dipstick test. Urinary chemokines were measured by MILLIPLEX MAP Human Cytokine/Chemokine Immunoassay and their association with UTI and OAB was determined by univariate and multivariate statistics. Significant elevation of CXCL-1, CXCL-8 (IL-8), and CXCL-10 together with reduced levels for a receptor antagonist of IL-1A (sIL-1RA) were seen in UTI relative to OAB and asymptomatic controls. Elevated CXCL-1 urine levels predicted UTI with odds ratio of 1.018 and showed a specificity of 80.77% and sensitivity of 59.68%. Postantibiotic treatment, reduction was seen in all CXC chemokines with a significant reduction for CXCL-10. Strong association of CXCL-1 and CXCL-10 for UTI over OAB indicates mechanistic differences in signaling pathways driving inflammation secondary of infection in UTI compared with a lack of infection in OAB. Urinary chemokines highlight molecular differences in the paracrine signaling driving the overlapping symptoms of UTI and OAB.

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

“…This current study restricted only to BPH patients negative for prostate cancer, as determined by prostate biopsy, found that increasing urine levels of CXCL‐10, CCL5, and CCL3 were marginally associated with the extent of inflammation and greater intensity of CD3 and CD20 lymphocytic infiltration in prostate tissue. Previous studies have reported that urine levels of CXCL‐10, CCL3, and CCL5 in healthy male asymptomatic control subjects are either undetectable or below the median values of BPH subjects reported here and elsewhere …”

“…Here, we noted that extent of prostatic inflammation in different biopsy cores of BPH patients was associated with the elevation of CXCL‐10 and the grade of inflammation was marginally with the elevated urine levels of CCL3. We have previously reported that elevated urine levels of CXCL‐10 are associated with acute and chronic inflammation in lower urinary tract . CCL3 and CCL2 were found elevated in expressed prostatic secretions of prostatitis patients .…”

“…Previous studies have reported that urine levels of CXCL-10, CCL3, and CCL5 in healthy male asymptomatic control subjects are either undetectable or below the median values of BPH subjects reported here and elsewhere. 20,22 One of the predisposing factor for BPH is the metabolic syndrome, 10 whose key determinant is the increased centralized deposition of adipose tissue. We found a broad and robust relationship between a key measure of centralized adiposity called waist-hip ratio and increased urine levels of sIL-1Ra.…”

“…The present study seeks to evaluate whether urinary chemokines can reflect the clinical attributes of BPH/LUTS patients. The selection of the chemokines for the present study was based on the known role of following chemokines CXCL‐1, CXCL‐8, CXCL‐10, CCL2, CCL3, and CCL5 in the chemoattraction of CD3+ and CD20+ lymphocytes and the reports on detection of other included proteins in the prostate tissue or biofluids of BPH patients or patients suffering from LUTS …”

Bladder overactivity involves overexpression of MicroRNA 132 and nerve growth factor

“…NGF content in homogenized tissue was determined using commercially available NGF Emax® ImmunoAssay System ELISA Kit (Promega, Madison, WI, USA) according to the manufacturer’s instructions. Intercellular Adhesion Molecule-1 sICAM-1(Othumpangat et al, 2012a) and monocyte chemoattractant protein-1 (MCP-1)(Tyagi et al, 2016) were analyzed by Luminex xMAP kit obtained from EMD Millipore (Billerica, MA) as previously described and calculations were expressed as pg/mg of protein.…”