Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics

Abstract

The objective of the present study was to investigate the diagnostic values of urine cytokines in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and to identify their correlations with clinical characteristics. Urine samples were collected from 127 patients with IC/BPS [European Society for the Study of Interstitial Cystitis (ESSIC) types 1 and 2] and 28 controls. Commercially available multiplex immunoassays (MILLIPLEX map kits) were used to analyze 31 targeted cytokines. Cytokine levels between patients with IC/BPS and controls were analyzed using ANOVA. Receiver-operating characteristic curves of each cytokine to distinguish IC/BPS from controls were generated for calculation of the area under the curve. Patients with IC/BPS had urine cytokine profiles that differed from those of controls. Between patients with ESSIC type 1 and 2 IC/BPS, urine cytokine profiles were also different. Among cytokines with high diagnostic values (i.e., area under the curve > 0.7) with respect to distinguish patients with ESSIC type 2 IC/BPS from controls, regulated upon activation, normal T cell expressed and presumably secreted (RANTES), macrophage inflammatory protein (MIP)-1β, and IL-8 were of higher sensitivity, whereas macrophage chemoattractant protein (MCP)-1, chemokine (C-X-C motif) ligand 10 (CXCL10), and eotaxin-1 were of higher specificity. In multivariate logistic regression models controlling for age, sex, body mass index, and diabetes mellitus, the urine cytokines with high diagnostic values (MCP-1, RANTES, CXCL10, IL-7, and eotaxin-1) remained statistically significant in differentiating IC/BPS and controls. MCP-1, CXCL10, eotaxin-1, and RANTES were positively correlated with glomerulation grade and negatively correlated with maximal bladder capacity. In conclusion, patients with IC/BPS had urine cytokine profiles that clearly differed from those of controls. Urine cytokines might be useful as biomarkers for diagnosing IC/BPS and mapping its clinical characteristics.

Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm

“…Niimi et al reported that urine CXCL10 was not increased in 25 non-Hunner type IC/BPS patients in compared with 31 controls 17 . However, in our previous study with 127 non-Hunner type IC/ BPS patients and 28 controls, urine CXCL10 levels were not only significantly increased in IC/BPS patients but also correlated with the glomerulation grade and maximal bladder capacity 11 . Eotaxin-1, acting as a selective chemoattractant for eosinophils, is implicated in many eosinophilic inflammatory diseases 18 .…”

“…MCP-1, CXCL10, and RANTES are known to be upregulated and involved in chemokine signaling in peripheral neuroinflammatory responses 16 . These cytokines were elevated in IC/BPS urine specimens, suggesting neuropathic inflammation, as well as afferent hypersensitivity within the bladder 11 . Niimi et al reported that urine CXCL10 was not increased in 25 non-Hunner type IC/BPS patients in compared with 31 controls 17 .…”

“…Eotaxin-1, acting as a selective chemoattractant for eosinophils, is implicated in many eosinophilic inflammatory diseases 18 . Elevated eotaxin levels in IC/BPS urine specimens suggest an autoimmune response and allergy-related inflammation in IC/BPS 1,11 . In the present study, these cytokines were increased in IC/BPS patients and remained statistically significant in differentiating IC/BPS from OAB in multivariate logistic regression models.…”

“…Urinalysis was performed simultaneously to confirm an infection-free status before urine samples were stored. The preparation of urine samples, the analytes used for investigation in urine samples, and the laboratory procedures were similar to those in our previous study 11 . Inflammation-related cytokines, chemokines, and neurotrophins in urine samples were assayed using commercially available microspheres with the Milliplex Human cytokine/chemokine magnetic bead-based panel kit (Millipore, Darmstadt, Germany).…”

“…The diagnostic criteria for IC/BPS, based on the proposed guidelines of the European Society for the Study of Interstitial Cystitis, constituted "chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder accompanied by at least one other urinary symptom, such as persistent urge to void or urinary frequency, for more than 6 months, " and the exclusion of potentially similar diseases 11,25 . All enrolled IC/BPS patients were European Society for the Study of Interstitial Cystitis type 2 (i.e.…”