MP78-04 PRO-FIBROTIC SERUM CYTOKINES ARE INCREASED IN PATIENTS WITH ANTERIOR URETHRAL STRICTURE DISEASE

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP78-04 PRO-FIBROTIC SERUM CYTOKINES ARE INCREASED IN PATIENTS WITH ANTERIOR URETHRAL STRICTURE DISEASE Wade Gutierrez, Yi Luo, Denise Juhr, Benjamin Breyer, Sean Elliott, Jeremy Myers, Alex Vanni, Katherine Christel, Laila Dahmoush, and Bradley Erickson Wade GutierrezWade Gutierrez More articles by this author , Yi LuoYi Luo More articles by this author , Denise JuhrDenise Juhr More articles by this author , Benjamin BreyerBenjamin Breyer More articles by this author , Sean ElliottSean Elliott More articles by this author , Jeremy MyersJeremy Myers More articles by this author , Alex VanniAlex Vanni More articles by this author , Katherine ChristelKatherine Christel More articles by this author , Laila DahmoushLaila Dahmoush More articles by this author , and Bradley EricksonBradley Erickson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003355.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Anterior urethral stricture disease (aUSD) is a heterogeneous condition with complex pathophysiology. Little is known about systemic factors predisposing to or resulting from stricture formation. To address this gap in knowledge, we assessed levels of 27 cytokines in serum from patients with and without strictures. We hypothesized that patients with strictures would have distinct serum cytokine profiles relative to controls. METHODS: Five centers prospectively enrolled patients into an NIDDK-funded study evaluating local and systemic inflammatory patterns in aUSD. Subjects underwent standard urethroplasty per surgeon routine and tissue was sent to a centralized tissue repository. Serum was collected prior to stricture repair. Levels of 27 cytokines were assessed by ELISA. H&E-stained sections of stricture tissue were examined by a single, blinded pathologist and evaluated for the presence or absence of inflammation. RESULTS: Patient-matched serum and stricture specimens were collected from 113 subjects. Strictures were grouped based on the presence or absence of inflammation (n=66 and n=47, respectively). Serum from age-matched patients without urethral strictures was used as a control (n=9). Four pro-fibrotic cytokines were significantly increased in patients with strictures: interleukin-9 (IL-9), platelet derived growth factor-BB (PDGF-BB), C-C Motif Chemokine Ligand 4 (CCL4), and C-C Motif Chemokine Ligand 5 (CCL5) [A-D]. Only IL-9 levels differed by stricture inflammatory pattern (890.4 ng/mL vs 773.0 ng/mL, p<0.05). In addition to higher levels of pro-fibrotic cytokines, interleukin-1 receptor antagonist (IL-1Ra), which has immunosuppressive functions, was increased in patients with strictures [E]. CONCLUSIONS: Patients with aUSD have unique serum cytokine profiles relative to age-matched controls. Four of these cytokines, IL-9, PDGF-BB, CCL4, and CCL5 have previously been implicated in promoting fibrosis and scarring in humans and in animal models. IL-1Ra has immunosuppressive functions and may be increased to maintain homeostasis. Further studies are needed to determine if these cytokines are increased as a result of the stricture or if their levels are higher at baseline, predisposing patients to stricture formation. Source of Funding: NIDDK 1R21DK115945-01 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1132 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wade Gutierrez More articles by this author Yi Luo More articles by this author Denise Juhr More articles by this author Benjamin Breyer More articles by this author Sean Elliott More articles by this author Jeremy Myers More articles by this author Alex Vanni More articles by this author Katherine Christel More articles by this author Laila Dahmoush More articles by this author Bradley Erickson More articles by this author Expand All Advertisement PDF downloadLoading ...