Presentation Authors: Norifumi Nishishita*, Kurashki, Japan, Shin Ohira, Kurashiki, Japan, Shigenobu Tone, Hiki-gun, Saitama, Japan, Ryoei Hara, Tomohiro Fujii, Shinya Uehara, Yoshiyuki Miyaji, Atsushi Nagai, Kurashiki, Japan
Introduction: Tadalafil (PDE5 inhibitor) is indicated for the treatment of benign prostatic hyperplasia with lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED). In previous research, Tadalafil shows anti-inflammatory action in the prostate. The evidence-based data for the treatment of Chronic prostatitis (CP) is lacking. We hypothesized that Tadalafil contribute to innovative therapy for the CP. To examine this hypothesis, we investigated anti-inflammatory effect of Tadalafil using all sorts of cytokines/chemokine in the CP model mice.
Methods: Ten to twelve weeks old C57BL/6 male mice were used through the study. Prostate gland extracted from Wister rat were used as PAg (concentration: 10mg / PBS1ml). PAg 100Î¼g / titer max adjuvant 100Î¼l were injected into mice subcutaneously (shoulder and tail). After CP modeling, systemic organs were obtained from individual mice up to 12 weeks every week. In preliminary examination, we confirmed the validity of CP model using comprehensive cytokines/chemokines assay in the systemic organs. Next, we administrated Tadalafil 25Î¼g / pure water 50Î¼l (oral) up to 12 weeks every day (control: pure water 50Î¼l / day). Histological changes were microscopically examined and evaluated using HE staining. Inflammatory changes in the CP model of Tadalafil administrated mice were analyzed using comprehensive cytokines/chemokines assay for determining representative candidates. Biochemical and immunohistochemical changes were analyzed using representative candidates. Series of these experiments were duplicated at least.
Results: Histological analysis showed that invasion of inflammatory cells and fibrosis of interstitial tissue were observed in the CP model of Tadalafil non-administrated mice compared with Tadalafil administrated mice. Prostatic structure in Tadalafil administrated mice were still maintained at week12 after PAg injection. Comprehensive cytokines/chemokines assay showed that significant decreased expression of ICAM-1 (only week1), M-CSF, IL-16, CCL2, CCL3, CXCL2, TREM-1 and TIMP-1 were observed in the CP model of Tadalafil administrated mice compared with that of t administrated Tadalafil non-administrated mice. Same results were obtained from biochemical and immunohistochemical analysis using separate quantitative assay and immunofluorescent staining.
Conclusions: Tadalafil contribute to suppression of macrophage-related inflammatory and fibrosis change of interstitial tissue. Therefore, Tadalafil is an effective therapy in the chronic prostatitis.