Can We Use Urinary Cytokine/Chemokine Analysis in Discriminating Ulcer-Type Interstitial Cystitis/Bladder Pain Syndrome?

Abstract

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) has ulcer (HIC) and non-ulcer subtypes. Differentiation of these two subtypes could only be based by cystoscopy. This study analyzed the urinary cytokines and chemokines among IC/BPS subtypes and controls for discriminating HIC from non-HIC and controls. Materials and Methods: A total of 309 consecutive patients with clinically diagnosed IC/BPS were enrolled. All patients received cystoscopic hydrodistention under anesthesia and urine samples were collected prior to the procedure. Enrolled patients were classified into subtypes based on the glomerulation grade, maximal bladder capacity (MBC), and presence of Hunner’s lesion. Inflammation-related cytokines and chemokines in urine samples, including interleukin-8 (IL-8), C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin-1 (eotaxin), IL-6, macrophage inflammatory protein-1 beta (MIP-1β), regulated upon activation, normally T-expressed, and presumably secreted (RANTES), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were assayed using commercially available microspheres with the Milliplex® Human Cytokine/Chemokine Magnetic Bead-based Panel kit. The clinical data and urine levels of analytes between IC/BPS patients and controls, and among HIC, non-HIC, and controls were analyzed. Results: Among the 10 proteins, MCP-1, eotaxin, MIP-1β, TNF-α, and PGE2 were significantly different between IC/BPS and control, while IL-8, CXCL10, BDNF, IL-6, and RANTES were significantly higher in HIC than non-HIC patients. The receiver operating characteristic curve was used to analyze each urine biomarker in the patients with IC/BPS and controls. Among the 10 urine biomarkers, MIP-1β and TNF-α had an area under curve of >0.70 to predict IC/BPS from controls, however, the predictive values of these urine biomarkers to predict HIC from non-HIC were low. Combined cut-off values of MIP-1β and TNF-α can only have a 50% sensitivity and 39.6% specificity in identifying HIC from non-HIC. Conclusion: The results of this study demonstrate that urine cytokines and chemokines may be useful to discriminate patients with HIC from controls. An elevation of urine levels of IL-8, CXCL 10, BDNF, IL-6, and RANTES in IC/BPS patients should prompt physicians to consider the diagnosis of HIC.