Effect of digital hypothermia on lamellar inflammatory signaling in the euglycemic hyperinsulinemic clamp laminitis model

J Vet Intern Med. 2020 Jul;34(4):1606-1613. doi: 10.1111/jvim.15835. Epub 2020 Jun 25.


Background: Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycemic hyperinsulinemic clamp (EHC) model of laminitis, but the protective mechanisms are unclear.

Hypothesis/objectives: To determine if CDH inhibits lamellar inflammatory signaling in the EHC model of laminitis.

Animals: Eight Standardbred horses.

Methods: Prospective experimental study. Horses underwent an EHC, with 1 forelimb treated with CDH and the other kept at ambient temperature (AMB). Horses were euthanized 48 hours after initiation of the EHC and lamellar tissue was analyzed via polymerase chain reaction (pro-inflammatory cytokine and chemokine genes-CXCL1, CXCL6, CXCL8, IL-6, MCP-1, MCP-2, IL-1β, IL-11, cyclooxygenase 1 and 2, tumour necrosis factor-alpha [TNF-α], E-selectin, and intercellular adhesion molecule-1 [ICAM-1]) and immunoblotting (phosphorylated and total signal transducer and activator of transcription 1 [STAT1] and STAT3).

Results: Compared to AMB, lamellar messenger ribonucleic acid (mRNA) concentrations of CXCL6 (P =.02), CXCL8 (P = .008), IL-6 (P = .008), IL-1β (P = .008), IL-11 (P = .008), and cyclooxygenase-2 (P = .008) were decreased in CDH. Cyclooxygenase-1 (P = .008) was increased in CDH, while CXCL1 (P = .15), MCP-1 (P = .05), MCP-2 (P = .46), TNF-α (P = .05), E-selectin (P = .15), and ICAM-1 (P = .15) mRNA were not significantly different. Compared to AMB, lamellar concentration of total STAT3 protein was decreased in CDH (P < .001), but there was no change in phosphorylated STAT3 (P-STAT3 [S727] P = .19; P-STAT3 [Y705] P = .05). There was no change in lamellar concentrations of total STAT1 (P = .75) or phosphorylated STAT1 (P-STAT1 [S727], P = .25; P-STAT1 [Y701], P = .64).

Conclusions and clinical importance: These data add further support for the use of CDH as a first aid treatment for severe acute laminitis associated with hyperinsulinemia in horses.

Keywords: endocrinopathic; horse; hypothermia; inflammation; insulin.

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Foot Diseases / chemically induced
  • Foot Diseases / physiopathology
  • Foot Diseases / veterinary*
  • Gene Expression Regulation
  • Glucose Clamp Technique / veterinary
  • Hoof and Claw / pathology*
  • Horse Diseases / chemically induced*
  • Horse Diseases / physiopathology
  • Horses
  • Hyperinsulinism / veterinary
  • Hypothermia, Induced / veterinary*
  • Inflammation / chemically induced
  • Inflammation / physiopathology
  • Inflammation / veterinary*
  • Male
  • Prospective Studies
  • Signal Transduction


  • Cytokines