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

• Published in: Pain (Amsterdam) Vol. 157; no. 3; pp. 585 - 597
• Main Authors: Motrich, Ruben D, Breser, María L, Sánchez, Leonardo R, Godoy, Gloria J, Prinz, Immo, Rivero, Virginia E
• Format: Journal Article
• Language: English
• Published: United States 01.03.2016
• Subjects: Animals; Cells, Cultured; Chronic Pain - metabolism; Chronic Pain - pathology; Disease Models, Animal; Inflammation - metabolism; Inflammation - pathology; Interleukin-17 - deficiency; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pelvic Pain - metabolism; Pelvic Pain - pathology; Prostatitis - metabolism; Prostatitis - pathology; Rats; Rats, Wistar
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1097/j.pain.0000000000000405

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 pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in 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. Moreover, 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 caused similar prostate inflammation and chronic pelvic pain. 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 PAg 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 not to be essential for pathology induction and chronic pelvic pain development.