Effect of digital hypothermia on lamellar inflammatory signaling in the euglycemic hyperinsulinemic clamp laminitis model.
Authors: Stokes Simon M, Burns Teresa A, Watts Mauria R, Bertin François-René, Stefanovski Darko, Medina-Torres Carlos E, Belknap James K, van Eps Andrew W
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary Continuous digital hypothermia (CDH) has proven effective at preventing lamellar structural failure during experimentally induced laminitis, yet the precise anti-inflammatory mechanisms responsible for this protection remain poorly understood. Researchers subjected eight Standardbred horses to a euglycemic hyperinsulinemic clamp—a controlled model that mimics insulin-associated laminitis—with one forelimb treated by CDH whilst the contralateral limb remained at ambient temperature; lamellar tissue was harvested 48 hours later and analysed for pro-inflammatory gene expression via polymerase chain reaction and protein signalling pathways via immunoblotting. CDH significantly suppressed key pro-inflammatory mediators, including chemokines CXCL6 and CXCL8, cytokines IL-6, IL-1β, and IL-11, and the inducible enzyme cyclooxygenase-2, whilst paradoxically increasing the constitutive cyclooxygenase-1—a pattern suggesting preferential dampening of acute inflammatory cascades without eliminating physiological homeostatic signalling. Total STAT3 protein concentrations were substantially reduced in cooled tissue, though phosphorylated STAT3 levels showed only marginal changes, indicating that CDH may suppress the pro-inflammatory transcription factor pool itself rather than simply blocking its activation. These findings reinforce CDH's role as an evidence-based therapeutic intervention for severe hyperinsulinaemic laminitis, providing a molecular framework for its clinical efficacy and supporting its early adoption in acute management protocols.
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Practical Takeaways
- •Digital hypothermia effectively suppresses the inflammatory cascade in hyperinsulinemic laminitis by down-regulating key pro-inflammatory cytokines and chemokines, supporting its use as a first-aid intervention in acute severe cases
- •The mechanism appears to involve reduced STAT3 signaling rather than altered STAT1, suggesting hypothermia may work through selective pathway inhibition rather than broad immunosuppression
- •This evidence supports implementing continuous digital cooling protocols early in cases of acute laminitis associated with metabolic syndrome, as it may prevent or delay lamellar failure through inflammatory control
Key Findings
- •Continuous digital hypothermia (CDH) significantly decreased lamellar mRNA expression of pro-inflammatory markers CXCL6, CXCL8, IL-6, IL-1β, IL-11, and cyclooxygenase-2 compared to ambient temperature control limbs (P ≤ 0.02)
- •CDH reduced total STAT3 protein concentration (P < 0.001) without altering phosphorylated STAT3 or STAT1 signaling pathways
- •Cyclooxygenase-1 mRNA was paradoxically increased in CDH-treated tissue (P = 0.008), while TNF-α, adhesion molecules (E-selectin, ICAM-1), and some chemokines (CXCL1, MCP-1, MCP-2) showed no significant difference