Th1 but not Th17 Cells are Essential for Prostate Inflammation and Chronic Pelvic Pain Development in an Experimental Model of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

MOTRICH, RD; BRESER, ML; SANCHEZ, L; GODOY, GJ; PRINZ, I; RIVERO, VE

Medellin

Congreso; 11th Congress of the Latin American Association of Immunology; 2015

Latin American Association of Immunology

Pain and inflammation in the absence of infection are hallmarks in Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) patients. Its etiology is unclear and autoimmunity has been proposed as a cause. Our laboratory has pioneered the development of Experimental Autoimmune Prostatitis (EAP) models that have reflected most disease features and have long been used for studying CP/CPPS. Herein, we studied the autoimmune response and prostate inflammation induction together with chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild type (C57BL/6) mice immunized with prostate antigens (PA) or saline (C). Animals were immunized on days 0 and 15. Pain was assayed as tactile allodynia using Von Frey filaments. Animals were euthanized and the specific immune response, prostate histopathology and infiltrating leukocytes were analyzed. Prostate antigen (PAg)-immunized C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4+ T cells and macrophages. In parallel, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response that caused similar prostate inflammation and chronic pelvic pain was observed. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion, and neither infiltration nor damage in the prostate. As observed in wild type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PA immunization, a Th1 associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines respectively diminishes or enhances EAP susceptibility. In addition, IL-17 showed to be dispensable for pathology induction and chronic pelvic pain development.