Effect of Sacral Neuromodulation on Outcome Measures and Urine Chemokines in Interstitial Cystitis/Painful Bladder Syndrome Patients.

OBJECTIVES: Sacral neuromodulation (SNM) may improve interstitial cystitis/painful bladder syndrome (IC/BPS) symptoms of urinary frequency, urgency and perhaps even pain, but objective measures of improvement are lacking. We evaluated the potential for urinary chemokines to serve as measures of treatment response over time to SNM. METHODS: Women with IC/BPS undergoing SNM consented for this study. Three-day bladder/pain diaries were collected at baseline and validated Interstitial Cystitis Symptom Problem Index (ICSPI) scores and mid-stream urine specimens were collected at baseline and at 24 weeks after successful implant. Collected urine was screened for infection by dipstick and analyzed for chemokines by luminex xMAP analysis. RESULTS: At baseline (n = 16), urine levels of CXCL-1 positively correlated with pain score (r = 0.63, P = 0.009), urgency (r = 0.61, P = 0.01), ICSPI (r = 0.43, P = 0.09) and daily voids (r = 0.44, P = 0.08). ICSPI and pain scores also positively correlated with sIL-1ra (r = 0.50, P = 0.04) and monocyte chemotactic protein-1 (MCP-1) or CCL2 positively correlated with daily voids (r = 0.45, P = 0.07) only. At 24 weeks, the median ICSPI index fell from 28 to 15 (n = 7, P = 0.008). Urine levels of sIL-1ra (633.8 ± 188.2 vs. 149.9 ± 41.62 pg/mL) and MCP-1 (448.3 ± 11.6 vs. 176.9 ± 46.16 pg/mL) and CCL5 (20.78 ± 4.09 vs. 11.21 ± 4.12 pg/mL) were also significantly reduced at the follow-up relative to baseline values (P = 0.04). Multivariable analysis of data revealed that sIL-1ra and MCP-1 together explained the majority of variance in data. Levels of CXCL-1, CXCL-10, interleukin (IL)-8, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) were also reduced at 24 weeks, but differences were not significant. CONCLUSIONS: Concomitant decrease in urine levels of chemokines especially MCP-1 was associated with treatment response of SNM. These results support the role of chemokines as downstream effectors of neuromodulation response and could serve as potential non-invasive measures of treatment response. CLINICAL TRIAL REGISTRATION NUMBER: NCT01739946.

The phytotherapeutic agent, eviprostat, suppresses stromal proliferation and inflammation even after establishment of nonbacterial prostatitis in the rat prostate.

OBJECTIVE: To evaluate the effect of phytotherapeutic agent, Eviprostat, administered after the establishment of nonbacterial prostatitis (NBP) on the stroma-to-epithelium ratio (S/E ratio), inflammatory scores, tissue macrophage infiltration, and cytokines and chemokines levels in prostate tissue and urine. MATERIALS AND METHODS: Ten-month-old male Wistar rats were castrated and exposed to 17-beta-isomer of estradiol for 30 days to induce NBP. Twenty-five NBP rats were divided into 5 groups: (1) NBP (0) rats sacrificed immediately after the establishment of NBP; (2,3) NBP (30)/control (CTL) and NBP (30)/Eviprostat (EVI) rats fed without or with 0.1% Eviprostat under estradiol-free for 30 days, respectively; and (4,5) NBP (60)/CTL and NBP (60)/EVI rats fed without or with 0.1% Eviprostat under estradiol-free for 60 days, respectively. The S/E ratio, inflammatory scores, and the number of macrophage infiltration in the prostate were assessed. Concentrations of cytokines and chemokines in prostatic tissue and urine were measured by enzyme-linked immunosorbent assay. RESULTS: The S/E ratio was significantly increased with time until 60 days under estradiol-free condition (P <.001). The S/E ratio and the inflammatory scores in NBP (60)/EVI was significantly lower than that of NBP (60)/CTL (P <.001, and P = .022, respectively). The mean tissue concentration of chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1) in NBP (60)/CTL was significantly higher than that in NBP (0) (P = .016), whereas, there was no difference between NBP (60)/EVI and NBP (0). Furthermore, urinary CCL2/MCP-1 was significantly decreased in NBP (60)/EVI as compared with NBP (0) (P = .028). CONCLUSION: Eviprostat suppresses the stromal proliferation and inflammation in the rat prostate after the establishment of NBP at least partly owing to inhibitory effect on CCL2/MCP-1 production in the prostate.

Effect of a phytotherapeutic agent, Eviprostat®, on prostatic and urinary cytokines/chemokines in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation in the prostate has recently been recognized as an important component of the symptom progression of benign prostatic hyperplasia. The objective of this study was to evaluate a range of cytokines/chemokines in prostate tissue and urine to identify markers of prostate inflammation in a prostatitis model and to investigate the effect of a phytotherapeutic agent, Eviprostat®, on these markers. METHODS: Ten-month-old male Wistar rats were divided into four groups. Nonbacterial prostatitis (NBP) was experimentally induced in groups 2-4 by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. Control rats were fed a standard diet, while animals in the Eviprostat groups were fed a diet containing 0.05 or 0.1% Eviprostat for 30 days. The levels of cytokines/chemokines in prostate tissue on the 31st day and in urine collected the day before castration and the day before removal of the prostate were determined. RESULTS: Experimentally induced NBP increased the prostatic levels of the cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The levels of the chemokines CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage inflammatory protein-1α (MIP-1α), CXCL1/CINC-1, CXCL3/CINC-2, and CXCL5/LIX were elevated in both prostate and urine. Eviprostat significantly suppressed the increases in prostate IL-1ß, TNF-α and CCL3/MIP-1α and prostatic and urinary CCL2/MCP-1 and CXCL1/CINC-1. CONCLUSIONS: Chemokines, including CCL2/MCP-1 and CXCL1/CINC-1, were elevated in the prostate and urine of NBP rats, and Eviprostat potently suppressed the increases in CCL2/MCP-1 and CXCL1/CINC-1. These chemokines are therefore candidate diagnostic biomarkers for nonbacterial chronic prostatic inflammation.