Seminal Plasma Cytokines and Chemokines in Prostate Inflammation: Interleukin 8 as a Predictive Biomarker in Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Benign Prostatic Hyperplasia

Abstract

ObjectiveThis prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. MethodsSeminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. ResultsSignificantly increased levels of cytokines (IL-1α, IL-1β, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164–2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630–19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033–5287] pg/ml; p=0.008), and BPH (5044 [3063–11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882±0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8–producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. ConclusionsIL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH.