title: 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 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.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba, Argentina Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Ruben D
authors.initials: RD
authors.lastname: Motrich
authors.forename: María L
authors.initials: ML
authors.lastname: Breser
authors.forename: Leonardo R
authors.initials: LR
authors.lastname: Sánchez
authors.forename: Gloria J
authors.initials: GJ
authors.lastname: Godoy
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Rivero
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D059350:Chronic Pain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D020381:Interleukin-17 / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017699:Pelvic Pain / Q000378:metabolism* / Q000473:pathology; D011472:Prostatitis / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020381:Interleukin-17