Immune remodeling in chronic prostatitis: from microenvironment imbalance to targeted therapy.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) imposes a substantial clinical burden through persistent pelvic pain, lower urinary tract symptoms, sexual and reproductive dysfunction, recurrence, and variable responses to empirical therapy. Although infection, pelvic floor dysfunction and neurogenic mechanisms remain relevant, accumulating evidence indicates that persistent immune remodeling and inflammatory microenvironmental imbalance provide a unifying framework for disease chronicity. This narrative review synthesizes current evidence linking epithelial and stromal stress, ROS accumulation, cytokine and chemokine networks, NF-κB, JAK/STAT, NLRP3, HMGB1, HIF-1α and CXCR4 signaling with macrophage reprogramming, Th17/Treg imbalance, myeloid-derived suppressor cell activity and neuroimmune pain. Rather than treating these events as isolated pathways, we emphasize their crosstalk within a self-sustaining inflammatory circuit that connects local tissue injury with systemic metabolic and microbiota signals. We also discuss controversies surrounding IL-10 expression, immune-event causality and the limited direct evidence for immune-cell subset heterogeneity in CP/CPPS. Future work should integrate longitudinal cohorts, single-cell and spatial multi-omics, immune phenotyping and mechanism-oriented clinical trials to move CP/CPPS management from symptom control toward stratified immune intervention.