Pd25-09 Toll-Like Receptor-2 (Tlr2) Underactivity Is Associated With Worse Urinary Symptoms in Interstitial Cystitis/Bladder Pain Syndrome (Ic/Bps)

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (PD25)1 May 2024PD25-09 TOLL-LIKE RECEPTOR-2 (TLR2) UNDERACTIVITY IS ASSOCIATED WITH WORSE URINARY SYMPTOMS IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME (IC/BPS) Abdul Baseet Arham, Andrew Schrepf, Yi Luo, Karl J. Kreder, and Michael A. O'Donnell Abdul Baseet ArhamAbdul Baseet Arham , Andrew SchrepfAndrew Schrepf , Yi LuoYi Luo , Karl J. KrederKarl J. Kreder , and Michael A. O'DonnellMichael A. O'Donnell View All Author Informationhttps://doi.org/10.1097/01.JU.0001008584.88541.ff.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A deep clinical phenotyping study investigating IC/BPS by the Multidisciplinary Approach to Pelvic Pain (MAPP) research network has previously shown that urinary frequency/urgency and pelvic pain, despite being hallmarks of IC/BPS, do not necessarily cluster together, suggesting independent mechanisms. TLR4 overactivity has been shown to strongly associate with pelvic pain but not urinary irritabilty. The purpose of this study was to investigate whether another TLR homologue, TLR2, would associate with urinary symptoms. METHODS: Sixty six IC/BPS subjects in the MAPP I study cohort were prospectively tested for peripheral blood, pro-inflammatory, Nuclear Factor kappa B (NFkB) cytokine responses to stimulation with the TLR2 agonist, SAC-1, a gram positive bacterial preparation from staphylococcus. In a later MAPP II study cohort, 153 IC/BPS subjects were similarly prospectively evaluated for whole blood NFkB cytokine responses to a related TLR2 agonist, FSL-1 (Fibroblast-stimulating Lipopeptide). RESULTS: Three TLR2-associated cytokines, Interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF) were significantly depressed in subjects with high baseline urinary frequency. (Figure 1). Similarly, subjects reporting the highest degree of urinary urgency to a controlled water ingestion provocation test, showed a significantly lower baseline TLR2/TLR4 ratio by global NFkB cytokine response while the lowest urgency was observed for those with the highest baseline TLR2/TLR4 ratios. (Figure 2). CONCLUSIONS: Relative TLR2 basal underactivity appears to associate with urinary frequency/urgency in two independent datasets. It remains to be seen whether efforts to enhance TLR2 responsiveness by using TLR2 agonists in IC/BPS patients will help ameliorate bladder irritability. Download PPTDownload PPT Source of Funding: NIH U01DK082344 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e539 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Abdul Baseet Arham More articles by this author Andrew Schrepf More articles by this author Yi Luo More articles by this author Karl J. Kreder More articles by this author Michael A. O'Donnell More articles by this author Expand All Advertisement PDF downloadLoading ...