Abstract

Benign prostatic hyperplasia (BPH) is a highly prevalent, age-associated condition characterized by nonmalignant 
enlargement of the prostate and a spectrum of lower urinary tract symptoms (LUTS). While androgen signaling 
and stromal–epithelial interactions are classic drivers of BPH, a large body of evidence now supports chronic, 
low-grade inflammation as a coequal engine of prostate growth and symptom progression. Inflammatory 
infiltrates in BPH tissue, typically macrophages, T cells, mast cells, and occasional neutrophils, create a 
cytokine-rich microenvironment that sustains epithelial and stromal proliferation, extracellular matrix (ECM) 
remodeling, angiogenesis, and smooth muscle hypercontractility. Cytokine networks rather than single mediators 
appear to determine biological outcomes: pro-growth and pro-fibrotic axes (eg, IL-6/STAT3, IL-8/CXCR 
signaling, TNF-α/NF-κB, IL-17–driven amplification loops, and TGF-β–mediated myofibroblast activation) 
intersect with counter-regulatory pathways (eg, IL-10, TGF-β immunoregulation, and specialized pro-resolving 
mediators) that may be insufficient or dysregulated in progressive disease. These immune signals interact with 
endocrine aging, metabolic syndrome, oxidative stress, local hypoxia, and recurrent infection or tissue injury, 
producing a “wound that does not heal” phenotype in the transitional zone. This review synthesizes current 
concepts on how cytokine networks shape the BPH microenvironment, linking immune cell recruitment and 
activation to prostate enlargement, fibrosis, and LUTS, and highlights emerging biomarker and therapeutic 
opportunities targeting inflammation-driven prostate growth.