Intravenous Injection of Sodium Hyaluronate Diminishes Basal Inflammatory Gene Expression in Equine Skeletal Muscle.
Authors: Gregg Savannah R, Barshick Madison R, Johnson Sally E
Journal: Animals : an open access journal from MDPI
Summary
# Intravenous Sodium Hyaluronate and Equine Muscle Inflammation Systemic hyaluronic acid (HA) is widely used in equine practice for joint inflammation, but its effects on skeletal muscle remain poorly characterised; this study investigated whether intravenous HA administration alters the inflammatory and repair response in working muscle. Six Thoroughbred geldings received weekly HA injections over three weeks before a submaximal exercise test, with gluteal muscle biopsies analysed via RNA sequencing before and one hour post-exercise, alongside assessment of HA localisation within muscle tissue. Horses receiving HA demonstrated significantly reduced baseline expression of leukocyte activity and cytokine production genes compared with controls, yet exercise-induced upregulation of inflammatory mediators proceeded normally in both groups—indicating that HA suppresses resting inflammation without blunting the necessary acute inflammatory response required for muscle repair. Gene markers for neutrophil and macrophage infiltration (NCF2 and CD163) increased post-exercise equally in both groups, whilst HA accumulation within muscle extracellular matrix was comparable between treatments, suggesting HA's anti-inflammatory effects operate through indirect mechanisms rather than local deposition. Notably, exercise promoted upregulation of tissue remodelling genes (CTGF, TGF-β1, MMP9, TIMP4, Col4A1) in both groups, confirming that HA does not suppress the adaptive repair cascade essential for training adaptation. For practitioners, these findings support routine HA use as an anti-inflammatory adjunct that reduces inflammatory tone without compromising the physiological processes underpinning training responses and tissue adaptation.
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Practical Takeaways
- •IV hyaluronate reduces basal inflammatory gene activity in resting muscle, which may contribute to its clinical anti-inflammatory reputation when used as a preventative treatment
- •HA does not blunt the muscle's necessary inflammatory response to exercise, meaning it won't interfere with normal repair and adaptation mechanisms
- •Current evidence supports the routine use of HA in performance horses, but benefits appear to be systemic modulation rather than direct localization to muscle tissue
Key Findings
- •HA-injected horses showed significantly fewer basal transcripts for leukocyte activity and cytokine production prior to exercise compared to controls
- •Exercise induced upregulation of cytokine genes and inflammatory markers (NCF2, CD163) equally in both groups, indicating HA does not suppress normal post-exercise inflammation
- •HA demonstrated no differences in localization to muscle extracellular matrix between treated and control horses
- •Genes associated with muscle remodeling (CTGF, TGF-β1, MMP9, TIMP4, Col4A1) were upregulated post-exercise, suggesting HA does not disrupt normal repair processes