IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome

Abstract

Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS)patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis(EAP)models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic paindevelopment in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization inC57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainlycomposed of CD41 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. Inimmunized IL-17-KOmice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation andchronic pelvic pain. Furthermore,markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronicpelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-typecontrol animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvicpain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and inducesprostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAPsusceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development