Anti-inflammatory effect of tadalafil, a phosphodiesterase 5 (PDE5) inhibitor, in autoimmune prostatitis

[ABSTRACT] Prostatitis is one of the most common diseases in urology. The pathology involves intricate interactions among multiple factors, and this has limited the establishment of evidence-based treatment for prostatitis. An autoimmune prostatitis mouse model has recently been suggested to be appropriate as a model of human prostatitis pathology. PDE5 inhibitors are indicated as therapy for benign prostatic hyperplasia with lower urinary tract symptoms, pulmonary arterial hypertension and erectile dysfunction, and have also been shown to have an anti-inflammatory effect against tissue inflammation. Thus, we hypothesized that a PDE5 inhibitor may have a preventive effect on prostatitis. To verify this hypothesis, the anti-inflammatory effects of a PDE5 inhibitor, tadalafil, were examined in an autoimmune prostatitis mouse model. C57BL/6 male mice aged 15 weeks were used in the study. Prostate glands from Wistar rats aged 5 weeks were used as a source of prostate antigen (protein concentration 10 mg/ml). Prostate antigen (100 μg in 100 μl of adjuvant) was subcutaneously injected into C57BL/6 mice. Tadalafil (25 μg in 50 μl of water) was orally administered every day for up to 10 weeks after establishment of the model. Control mice received water only (50 μl). Inflammatory changes were investigated using histological, biochemical and immunohistochemical analyses. Histological analysis using hematoxylin-eosin and Masson-Trichrome staining showed inhibitory effects on tissue fibrosis following invasion by inflammatory cells in tadalafil-treated mice compared with control mice. Biochemical and immunohistochemical analyses using an inflammation-related proteome assay and immunostaining showed decreased levels of M-CSF, TREM-1, TIMP-1, CCL2, CCL3 and CXCL2 in tadalafil-treated mice compared with control mice. Tadalafil has an inhibitory effect on tissue fibrosis and decreases cytokine levels after an inflammatory response. These results suggest that PDE5 inhibitors might be effective as therapy for prostatitis.