Experimental Autoimmune Prostatitis: the role of IFN-gamma

R. D. MOTRICH, E. VAN ETTEN, C. M. RIERA, C. MATHIEU, V. E. RIVERO

Rio de Janeiro, Brasil

Congreso; 13th International Congress of Immunology; 2007

IUIS

Autoimmune prostatitis has been proposed as a cause of Chronic-Pelvic-Pain-Syndrome. An autoimmune response against prostate antigens of a Th1-associated pattern was evidenced in humans and animal models. This work aimed to establish the role of IFN-ã in Experimental Autoimmune Prostatitis (EAP), by studying mice defficient in crucial transcription factors in the IFN-ã-signalling cascade: IRF-1 and STAT-1. EAP development was analyzed in C57BL/6, IRF1-KO and STAT1-KO mice as well as in the autoimmune prone NOD mouse model. EAP was induced by the immunization with Prostatein (PSBP) in CFA, while control mice received saline solution plus CFA. PSBP-immunized NOD mice evidenced severe mononuclear cell infiltration and lessions in prostatic tissue. In parallel, RT- PCR analysis of prostatic tissue revealed a significant increase in IFN-ã and IL-12 levels, and a decrease in IL-10 levels. A strong PSBP-specific cellular and humoral autoimmune response, with high IFN-ã secretion and IgG2a autoantibodies, were revealed. In contrast, reduced PSBP-specific T cell lymphoproliferation with decreased IFN-ã secretion was detected in autoimmune IRF1-KO and STAT1-KO mice when compared to C57BL/6 wild-type mice. Although the humoral autoimmune response was high, it wascharacterized by high titers of IgG1 and no specific IgG2a. Finally, PSBP-immunized IRF1-KO and STAT1-KO mice evidenced absent to mild inflammation in prostatic tissue, demonstrating that the autoimmune response developed by these animals was incapable of inducing the typical prostatic lessions of the EAP. In conclusion, these findings support a key role of IFN-ã in the pathogenesis of EAP.