Mapping the cytokine profile of painful bladder syndrome/interstitial cystitis in human bladder and urine specimens

Abstract

This study investigated the cytokine profile in bladder tissue and urine of painful bladder syndrome/interstitial cystitis (PBS/IC) patients. Multiplex analysis of 23 cytokines was performed with a multiple antigen bead assay (Luminex 100 IS) on cold cup bladder biopsy and urine specimens collected during cystoscopy with hydrodistention (HD) under general anesthesia from 10 PBS/IC patients (ICS definition). Collected tissue specimens and urine from pre-HD and post-HD (mean 27days) were compared to banked urine and tissue specimens (n=10) collected from control subjects without PBS/IC symptoms. Univariate comparison of bladder tissue levels found significant elevation of IL-16, IL-18, CTACK, ICAM-1, MCP-3, SCGFβ, TRAIL, and VCAM-1 in PBS/IC relative to controls. Multivariate analysis revealed VCAM-1 and ICAM-1 were responsible for the discrimination of both tissue and urine of PBS/IC from controls. Urine levels of MCP-3 and TRAIL were significantly reduced a month after HD in concert with improvement in standardized measures of clinical symptoms (pain, urgency, and frequency (PUF) overall score [mean 25.8±5.5 vs. 20.3±7, p=0.04] and symptom score [mean 18.2±3.2 vs. 12.2±5.9; p=0.009]). Post-HD urine levels of MCSF(r=0.88; p=0.003), MCP-3 (r=0.81; p=0.01), SDF1α (r=0.82; p=0.01), and IL-18 (r=0.64; p=0.08) positively correlated with improved symptom scores. These results indicate significant elevation of cytokines in PBS/IC bladder tissue relative to controls. Significant reduction in post-HD urine levels of MCP-3 and TRAIL relative to pre-HD in PBS/IC was associated with clinical improvement (as measured by PBS/IC symptom scores) to qualify them as biomarker candidates.