Urine chemokine levels correlate with treatment response to phosphodiesterase 4 inhibitor in prostatitis

AIM To investigate the association of urinary chemokines with the treatment response in chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) patients.METHODS Between 2007-2011,18 out of 21 male CP/CPPS patients met the exclusion/inclusion criteria of the 16 wk longitudinal study on twice daily oral treatment with Phosphodiesterase 4 inhibitor called Apremilast for 12 wk. Symptom scores and urine specimen were collected at baseline and every visit at 4 wk interval from CP/CPPS patients who completed at least 8 wk of drug treatment. Urine collected at each visit was frozen and then analyzed together after thawing for chemokines and growth factors using MILLIPLEX? MAP immunoassay. Cross sectional association of Chronic Prostatitis Symptom Index(CPSI) and visual analog scale(VAS) with chemokine levels in urine collected at baseline was assessed in 18 CP/CPPS patients relative to 10 asymptomatic male subjects. Longitudinal association between urine chemokine levels and symptom scores was assessed in 8 treatmentadherent CP/CPPS patients at baseline and at 4,8,12 and 16 wk.RESULTS Urine chemokines levels of CXCL-1(GRO-a),CXCL-8(IL-8),CXCL-10(IP-10) and CCL5(RANTES) in CP/CPPS patients at baseline were significantly elevated relative to asymptomatic subjects,whereas levels of s IL-1RA in CP/CPPS were significantly lower compared to controls(P <0.05). Quantitatively,urine levels of CXCL-10 were higher than other chemokines in CP/CPPS,but its fold change of5 relative to controls was lower than the 20 fold change noted for CXCL-8. The mean age of enrolled patients who completed at least 8 wk of treatment(n = 8) was 46.5± 9.4 years and analysis found that elevation of CXCL-8and CCL5 increased the odds for higher score of CPSI by54% and 25%,respectively(F test,P = 0.00007). Urine levels of CCL2(MCP-1) and CXCL-10 together explained approximately 85% of variance in longitudinal data on multivariate analysis. Bivariate analysis of 5 patients who fully complied and completed the assigned dose regimen,showed strong linear correlation of reduced urine levels of CXCL-10,CXCL-8,CCL5,CCL2 and PDGF with improvement in clinical activity as measured by pain VAS and CPSI(Pearson r = 0.83-0.97; P < 0.05).CONCLUSION Urine levels of CXCL-10,CCL2 and PDGF can be sensitive,objective and non-invasive markers of response to new therapeutic intervention in CP/CPPS patients.