Poster Presentation

Poster D in Poster Session D: Wednesday, August 5, 2:00 – 3:45 pm, Kimmel Center, Shorin & Rosenthal Rooms

Interleukin-6 Trans-Signaling as the Primary Cytokine Mechanism Linking Urinary Tract Inflammation to Cognitive Dysfunction

Saket Ram Ganti¹; ¹San Joaquin Delta College

Presenter: Saket Ram Ganti

Urinary tract infections (UTIs) and urethritis are highly prevalent peripheral inflammatory conditions whose neurological consequences remain undercharacterized at the cytokine level. Multiple pro-inflammatory mediators are upregulated during urogenital infection, yet few studies have systematically evaluated the relative mechanistic contributions of individual cytokines to cognitive dysfunction. Building on prior computational work linking urethritis-induced neuroinflammatory cascades to cognitive decline, we present a narrative review examining interleukin-6 (IL-6) in the context of urogenital inflammation and associated neurological outcomes. IL-6 exhibits a distinct signaling profile through trans-signaling, wherein binding to soluble IL-6 receptor (sIL-6R) enables activation of gp130 on cells lacking membrane-bound IL-6 receptor, including cerebrovascular endothelial cells. This pathway provides a potential mechanism for peripheral inflammatory signals to influence blood–brain barrier (BBB) function and central nervous system homeostasis. Across multiple inflammatory models, IL-6 signaling has been implicated in cognitive impairment, neuroinflammation, and BBB disruption, while selective inhibition of IL-6 trans-signaling using sgp130Fc has been shown to improve cognitive outcomes and preserve BBB integrity without suppressing classical IL-6 signaling. Collectively, these findings support a model in which IL-6 acts as a central mediator linking peripheral urogenital inflammation to neurocognitive dysfunction, and suggest that the IL-6/sIL-6R/gp130 axis represents a promising therapeutic target for neuroprotection.

Topic Area: Development, Individual Differences & Clinical Populations