E14 - Proteomic Signatures of Lipopolysaccharide-induced Systemic Inflammation in Horses

Abstract: Background Systemic inflammatory response syndrome (SIRS) in horses can lead to severe complications, including organ failure, vascular thrombosis, and laminitis. Currently, management relies primarily on supportive care such as fluid therapy and antibiotics. This approach persists largely because the underlying molecular mechanisms remain poorly understood. Objective Our primary objective is to characterize proteomic alterations associated with systemic inflammation using a controlled SIRS model. Methods Six healthy adult horses were enrolled in a randomized crossover study utilizing a lipopolysaccharide (LPS) infusion model to induce systemic inflammation. Horses received a 60 ng/kg LPS bolus, and endotoxemia was confirmed by neutropenia and development of SIRS criteria (tachycardia, tachypnea, hyperthermia). Plasma samples were collected at baseline and post-LPS challenge and analyzed using the SEER proteomics workflow. Differential protein expression between LPS-induced and baseline states was assessed, followed by functional enrichment analysis. Additionally, one horse with naturally occurring clinical SIRS was evaluated with samples collected at disease onset and resolution. Results Of 4,560 quantified proteins, 51 were significantly altered (26 upregulated, 25 downregulated; p < 0.05). Upregulated proteins were enriched in pathways related to angiogenesis, immune signaling, and extracellular matrix remodeling. Downregulated proteins were associated with cytoskeletal regulation, immune signaling, mucosal signaling, and MAPK signaling. The clinical horse’s proteomic profile mirrored that of LPS-challenged horses during active disease and resembled baseline profiles at recovery. Conclusions LPS-induced SIRS in horses triggers distinct proteomic changes involving vascular remodeling and immune activation, highlighting potential biomarkers and therapeutic targets for managing systemic inflammation in equine SIRS.