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.

Chronic prostatitis/chronic pelvic pain syndrome and prostate cancer: study of immune cells and cytokines

“…The numbers of macrophages/monocytes correlated significantly with the peroxidase positive leukocyte counts and IL‐8, IL‐6, and polymorphonuclear elastase levels in semen of CP/CPPS patients . PAg immunization in C57BL/6 mice prompted severe cell infiltration, mainly composed of CD4 + T cells and macrophages .…”

“…IL‐23 secreted chiefly by activated dendritic cells stimulates Th17 cells proliferation and secretion of IL‐17. The pain and inflammation of prostate gland without having the infection are the hallmarks of patients of CP/CPPS . IL‐17A/F is not essential for inflammation and chronic pelvic pain development in CP/CPPS model.…”

“…The pain and inflammation of prostate gland without having the infection are the hallmarks of patients of CP/CPPS . IL‐17A/F is not essential for inflammation and chronic pelvic pain development in CP/CPPS model. After CP/CPPS induction, non‐obese diabetic (NOD) mice developed a specific cellular response characterized by a mixed Th1/Th17 pattern that infiltrated and damaged the prostate.…”

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice

“…EAP is a frequently used animal model for CP/CPPS due to similar pathological features to those in CP/CPPS patients 19 . In this study, we established the mouse model of EAP following the same procedure as previously reported 20 .…”

Kronik Prostatit/Kronik Pelvik Ağrı Sendromunda Etyoloji ve Tanı

“…Lokal olarak prostatta meydana gelen patoloji doku düzeyinde hassasiyet ve basınç oluşturmaktadır. Burada bahsedilen sitokinler ve kemokinler hücre sinyal molekülleridir ve gerek proinflamatuar, gerek inflamatuar gerekse de onarım sürecinde yer alan çok sayıda alt başlıkta incelenmektedir (45)(46)(47)(48)(49)(50). Bu hücre sinyalleri aracılığı ile lökositler artmakta ve ekstraprostatik sekresyonda (EPS) saptanmaktadır.…”