Sphingosine 1-phosphate receptor modulator FTY720 suppresses rat experimental autoimmune prostatitis

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of male sex accessory glands and is characterized by a cellular and humoral prostate-specific autoimmune response associated with inflammatory mononuclear cell (MNC) infiltration. EAP shares important clinical and immunological features with human chronic prostatitis and chronic pelvic pain syndrome. Using immunohistochemistry, we determined the pattern of pathological changes during rat EAP development, regarding the cellular responses and infiltration into the prostate gland, and therapeutic effect of FTY720, a modulator of sphingosine-1-phosphate receptors which has shown promising protective effects in animal models and clinical trials of several autoimmune diseases. Significant accumulations of total MNCs, pan-T cells and CD8(+) cells were observed in prostatic stroma as early as 11 days after autoimmune induction. However, accumulation of reactive macrophages became significant 4 days later. After reaching the maximal level at Day 16, the accumulations of all the different cell populations fell back rapidly and returned to normal level by Day 35. Suppressive FTY720 significantly reduced inflammatory infiltration of different immune cell populations and tissue disruption in prostate of EAP rats. Our results therefore suggest that FTY720 might be a potential candidate for treatment of inflammatory prostatitis.