Progression of
benign prostatic hyperplasia (BPH) involves chronic
inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate
inflammation and tissue remodeling are exacerbated by
hypogonadism and prevented by
testosterone supplementation. We now investigated whether, in humans,
hypogonadism was associated with more severe BPH
inflammation and the in vitro effect of the selective
androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in
prostatectomy specimens from a cohort of BPH patients and correlation with serum
testosterone level was performed. Even after adjusting for confounding factors,
hypogonadism was associated with a fivefold increased risk of intraprostatic
inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (
tumor necrosis factor α,
lipopolysaccharide, or CD4(+)T cells) induced abundant secretion of inflammatory/
growth factors (
interleukin 6 (
IL6),
IL8, and
basic fibroblast growth factor (bFGF)). Co-culture of CD4(+)T cells with hBPH cells induced secretion of Th1 inducer (
IL12), Th1-recruiting
chemokine (
interferon γ inducible
protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific
cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/
growth factors, with the most pronounced effects on
IL8,
IL6, and bFGF. Reduced inflammatory
cytokine production by T-cells, an increase in
IL10, and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on
testosterone cells [corrected]. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.