MP47-18 LOW TESTOSTERONE ELEVATES PRO-INFLAMMATORY INTERLEUKIN FAMILY CYTOKINES: A POSSIBLE MECHANISM FOR THE POTENTIATION OF VASCULAR DISEASE IN ANDROGEN DEFICIENT MALES

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2014MP47-18 LOW TESTOSTERONE ELEVATES PRO-INFLAMMATORY INTERLEUKIN FAMILY CYTOKINES: A POSSIBLE MECHANISM FOR THE POTENTIATION OF VASCULAR DISEASE IN ANDROGEN DEFICIENT MALES Brian Freeman, Deidra Mountain, Timothy Brock, Jason Chapman, Stacy Kirkpatrick, Joshua Arnold, Scott Stevens, Mitchell Goldman, Frederick Klein, Michael Freeman, and Oscar Grandas Brian FreemanBrian Freeman More articles by this author , Deidra MountainDeidra Mountain More articles by this author , Timothy BrockTimothy Brock More articles by this author , Jason ChapmanJason Chapman More articles by this author , Stacy KirkpatrickStacy Kirkpatrick More articles by this author , Joshua ArnoldJoshua Arnold More articles by this author , Scott StevensScott Stevens More articles by this author , Mitchell GoldmanMitchell Goldman More articles by this author , Frederick KleinFrederick Klein More articles by this author , Michael FreemanMichael Freeman More articles by this author , and Oscar GrandasOscar Grandas More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1471AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Androgen deficiency (AD) is associated with increased risk of atherosclerosis, cardiovascular and peripheral arterial disease. Molecular mechanisms underlying this risk remain unclear. Matrix metalloproteinases (MMP) are enzymes largely responsible for vascular remodeling. We hypothesize that AD is a pro-inflammatory modulator, contributing to dysfunctional vascular remodeling. Here we investigated the role of testosterone in the modulation of inflammatory and MMP regulatory mechanisms. Methods Aged orchiectomized male rats underwent testosterone (TST) supplementation per controlled release pellet implantation (0-150mg). Young and aged intact groups served as controls. Serum was collected 0-28d post-implantation and analyzed by ELISAs, qualitative cytokine screening arrays, and quantitative multiplex analyses. Results When compared with TST levels in young, aged intact (AI), and placebo controls (2.72±0.35, 2.31±0.66, 0.15±0.07ng/ml, respectively), sub-physiological, physiological, and supra-physiological TST levels were achieved with 0.5, 2.5, and 35mg pellet implants (0.37±0.09, 2.89±0.44, 13.45±0.65ng/ml, respectively) per ELISA. Qualitative inflammatory cytokine screening arrays indicated interleukin family cytokines were elevated in the absence of TST. Quantitative multiplex analysis confirmed interleukin family regulation, with significant elevation of IL-2, IL-6, IL-10, IL-12, and IL-13 at sub-physiological TST levels (P<0.05; n=6), while increasing TST supplementation decreased interleukins in a dose-dependent manner approaching basal young and AI levels. G-CSF, TNFá, and INFã were also significantly elevated at sub-physiological levels (P<0.05; n=6). ELISA indicated MMP-9 was significantly decreased in AI vs. young (25.2±2.4, 53.1±8.6ng/ml; P<0.05; n=6), while supra-physiological levels significantly elevated MMP-9 (72.0±17.9ng/ml). MMP inhibitor TIMP-1 was decreased in AI and placebo vs. young, while supra-physiological TST increased TIMP-1. Conclusions Interleukin family cytokines, G-CSF, TNFá and INFã were elevated in groups with low testosterone, and MMP levels were differentially regulated by testosterone. These results suggest a correlation between AD and a pro-inflammatory environment. AD may play a role in vascular pathogenesis via regulation of inflammatory cascades. Future studies will examine the role of AD in inflammatory cytokine and MMP-modulated hyperplasia development in animal models. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e525 Peer Review Report Advertisement Copyright & Permissions© 2014MetricsAuthor Information Brian Freeman More articles by this author Deidra Mountain More articles by this author Timothy Brock More articles by this author Jason Chapman More articles by this author Stacy Kirkpatrick More articles by this author Joshua Arnold More articles by this author Scott Stevens More articles by this author Mitchell Goldman More articles by this author Frederick Klein More articles by this author Michael Freeman More articles by this author Oscar Grandas More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...