MP16-17 IL7, A PRIMARY MEDIATOR OF T-CELL DIFFERENTIATION, IS CORRELATED WITH PAIN IN BOTH CPPS PATIENTS AND EXPERIMENTAL AUTOIMMUNE PROSTATITIS (EAP) IN MICE (2014)

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Prostate & Genitalia1 Apr 2014MP16-17 IL7, A PRIMARY MEDIATOR OF T-CELL DIFFERENTIATION, IS CORRELATED WITH PAIN IN BOTH CPPS PATIENTS AND EXPERIMENTAL AUTOIMMUNE PROSTATITIS (EAP) IN MICE Stephen Murphy, Joesph Done, Praveen Thumbikat, and Anthony Schaeffer Stephen MurphyStephen Murphy More articles by this author , Joesph DoneJoesph Done More articles by this author , Praveen ThumbikatPraveen Thumbikat More articles by this author , and Anthony SchaefferAnthony Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.590AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The etiology of chronic pelvic pain syndrome (CPPS) is unknown but is thought to involve pro-inflammatory and autoimmune mechanisms. Previous investigations have highlighted a role for mediators of inflammation in disease progression by correlating levels of certain cytokines and chemokines with patient score. While these are informative in delineating the drivers of pathology, little has been done to demonstrate their role in causation. Mouse models of CPPS have been developed to attempt to understand the mechanism of these biomarkers in driving pain in humans. Here using both patient samples and the murine EAP model of CPPS we identify a novel cytokine that is increased in patients compared to controls and is associated with increased pain. This cytokine, namely IL7, is fundamental to the development of mature T-cell subsets and has roles in the disease pathogenesis of multiple sclerosis. It has also been identified as a key player in coordinating the maturation of auto-reactive T-cells, which can result in chronic autoimmunity. These findings highlight the role of T-cells in driving pain and indicate that differentiation and activation of lymphocytes may be key to development of autoimmunity. METHODS A multiplex cytokine array was performed using EPS samples from 33 patients and 8 controls. Levels of 41 chemokines and cytokines were assayed and total protein differences calculated. A combination of linear regression and correlation analyses was used to compare levels of cytokine with increasing levels of pain, urinary, QOL and Total scores, as assessed by NIH-CPSI questionnaire. Data from this study was then confirmed in murine EAP by QRTPCR, western and IHC staining. RESULTS Analysis of EPS samples from patients and controls revealed increases in levels of IL7, TNFa and GRO-a. Linear regression and correlation analysis revealed a positive association with increased levels of IL7 and pain, urinary, QOL and total scores and a negative correlation between decreased IL1RA levels and only QOL and Total scores. These results were mirrored in the murine EAP model in C57BL/6 mice. By QRTPCR we show increased IL7 in prostate and iliac lymph node tissue but not in bladder or spleen. Patient data was also confirmed at the protein level by IHC and western. CONCLUSIONS The T-cell differentiation factor IL7 is increased in patient EPS samples and these increased levels are correlated with increased pain, in both patients and murine models. These findings highlight the fundamental role of T-cell development in mediating pain in CPPS. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e159-e160 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Stephen Murphy More articles by this author Joesph Done More articles by this author Praveen Thumbikat More articles by this author Anthony Schaeffer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...