Disparate effects of LPS infusion and carbohydrate overload on inflammatory gene expression in equine laminae.
Authors: Kwon, Moore, Robertson, Hurley, Wagner, Vandenplas
Journal: Veterinary immunology and immunopathology
Summary
# Editorial Summary Endotoxemia has long been implicated in acute laminitis, particularly in hospitalised horses with gastrointestinal disease, yet the precise mechanisms remain poorly understood. Kwon and colleagues conducted a controlled comparison of two established laminitis models—lipopolysaccharide (LPS) infusion and carbohydrate overload—measuring clinical signs, circulating inflammatory cytokines (TNF-α and IL-10), and expression of 20 inflammation-associated genes within laminar tissue across four groups of horses (control, LPS-treated, carbohydrate developmental, and carbohydrate-lame). Surprisingly, LPS infusion triggered robust systemic inflammation with rapid elevation of TNF-α and IL-10 and marked leukopenia, but produced no detectable changes in laminar gene expression and crucially, no clinical laminitis; conversely, carbohydrate overload induced delayed systemic inflammatory responses alongside dramatic upregulation of inflammatory genes in laminar tissue and clinical laminitis development. These findings challenge the assumption that endotoxin is the primary driver of laminar pathology, suggesting instead that local tissue inflammation within the hoof laminae develops through mechanisms distinct from circulating endotoxemia. For practitioners, this distinction has important implications: systemic endotoxaemia alone may not trigger the cascade of local inflammatory gene expression characteristic of developmental laminitis, pointing toward metabolic and nutritional factors as more direct culprits in disease pathogenesis.
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Practical Takeaways
- •Endotoxemia may not be the primary driver of laminar tissue inflammation in laminitis—focus on controlling dietary carbohydrate intake and managing gastric dysbiosis in at-risk horses
- •Laminitis development involves local laminar tissue responses beyond systemic inflammation, suggesting that therapies targeting only circulating endotoxins may be insufficient
- •In hospitalized horses with gastrointestinal disease, consider that dietary management and carbohydrate fermentation may pose greater laminitis risk than endotoxin translocation alone
Key Findings
- •LPS infusion induced systemic inflammation with rapid TNF-α and IL-10 increases but produced no changes in laminar tissue inflammatory gene expression
- •Carbohydrate overload induced delayed systemic inflammation and marked increases in laminar tissue expression of 20 inflammation-associated genes
- •Only carbohydrate-overloaded horses developed clinical signs of laminitis (Obel grade I), despite both LPS and CHO groups showing systemic inflammatory responses
- •Laminar tissue inflammatory gene expression changes during acute laminitis development are mediated by factors other than endotoxin alone