title: Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model.
abstract: BACKGROUND
  The pathophysiological events inhibited by prophylactic digital hypothermia that result in reduction of the severity of acute laminitis are unknown.
  
  
  OBJECTIVE
  To determine if digital hypothermia inhibits lamellar inflammatory signalling during development of oligofructose (OF) induced laminitis.
  
  
  METHODS
  Fourteen Standardbred horses were given 10 g/kg bwt OF by nasogastric tube with one forelimb (CRYO) continuously cooled by immersion in ice and water and one forelimb (NON-RX) at ambient temperature. Lamellae were harvested prior to the onset of lameness (24 h post OF administration, DEV group, n = 7) or at the onset of lameness (OG1 group, n = 7). Lamellar mRNA was purified and cDNA produced for real time-quantitative PCR analysis of mRNA concentrations of cytokines (IL-6, IL-1β, IL-10), chemokines (CXCL1, CXCL6, CXCL8/IL-8, MCP-1, MCP-2), cell adhesion molecules (ICAM-1, E-selectin), COX-2 and 3 housekeeping genes. Data were analysed (NON-RX vs. CRYO, NON-RX vs. archived control [CON, n = 7] lamellar tissue) using nonparametric tests.
  
  
  RESULTS
  Compared with CON, the OG1 NON-RX had increased (P<0.05) lamellar mRNA concentrations of all measured mediators except IL-10, IL-1β and MCP-1/2, whereas only CXCL8 was increased (P<0.05) in DEV NON-RX. Within the OG1 group, CRYO limbs (compared with NON-RX) had decreased (P<0.05) mRNA concentrations of the majority of measured inflammatory mediators (no change in MCP-1 and IL-10). Within the DEV group, mRNA concentrations of CXCL-1, ICAM-1, IL-1β, CXCL8 and MCP-2 were decreased (P<0.05) and the anti-inflammatory cytokine IL-10 was increased (compared with NON-RX limbs; P<0.05).
  
  
  CONCLUSIONS
  Digital hypothermia effectively blocked early lamellar inflammatory events likely to play an important role in lamellar injury including the expression of chemokines, proinflammatory cytokines, COX-2 and endothelial adhesion molecules.
  
  
  CONCLUSIONS
  This study demonstrates a potential mechanism by which hypothermia reduces the severity of acute laminitis, and may help identify molecular targets for future laminitis intervention.
authors: Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Queensland, Australia.
authors: A W
authors: AW
authors: van Eps
authors: B S
authors: BS
authors: Leise
authors: M
authors: M
authors: Watts
authors: C C
authors: CC
authors: Pollitt
authors: J K
authors: JK
authors: Belknap
mesh_terms: D000818:Animals; D003080:Cold Temperature; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005534:Foot Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000662:veterinary*; D005786:Gene Expression Regulation; D006724:Hoof and Claw; D006734:Horse Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006736:Horses; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000662:veterinary*; D008297:Male; D009844:Oligosaccharides / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D009844:Oligosaccharides; C120489:oligofructose