Immune-cell imbalance and immunometabolic reprogramming in chronic prostatitis/chronic pelvic pain syndrome
TL;DR
A narrative review uses immune cells as its organizing axis and synthesizes recent evidence from single-cell sequencing, Mendelian randomization, and multi-omics to discuss candidate strategies involving the NLRP3 inflammasome, chemokine receptors, microbiota-derived metabolites, neuromodulation, and local or multi-component approaches.
Abstract
Available evidence suggests that disruption of immune homeostasis may contribute to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) beyond the effects of localized infection. This narrative review uses immune cells as its organizing axis and synthesizes recent evidence from single-cell sequencing, Mendelian randomization, and multi-omics. The available findings suggest that the M1/M2 dichotomy may not fully capture macrophage heterogeneity in prostatic tissues and that activation of the NLRP3 inflammasome and IL-1β release may form a candidate link between innate immunity and the Th17 response. On this basis, the review discusses how glycolytic and oxidative-stress-related reprogramming may shape immune-cell states; considers chemokine networks such as CCL5/CCR5 and CXCL10/CXCR3 in the recruitment of macrophages, Th1 cells, and Th17 cells to prostatic tissue; and examines how mast cells and neurogenic inflammation may participate in the bidirectional neuro-immune dialogue associated with persistent pain. At the intervention level, we distinguish human clinical observations and interventions from findings in cell systems and animal models, and discuss candidate strategies involving the NLRP3 inflammasome, chemokine receptors, microbiota-derived metabolites, neuromodulation, and local or multi-component approaches. These concepts require prospective validation in clinically defined CP/CPPS subgroups before they can support mechanism-guided treatment.