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Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model.
Abstract: 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.
© 2011 EVJ Ltd.
Publication Date: 2011-09-05 PubMed ID: 21895750DOI: 10.1111/j.2042-3306.2011.00416.xGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the effects of digital hypothermia in reducing the severity of acute laminitis in horses. The results show that digital hypothermia effectively blocks early lamellar inflammatory events that play a crucial role in lamellar injury.
Introduction and Methodology
- The study aimed to understand whether digital hypothermia can inhibit inflammatory signalling in the lamellae, a tissue layer in horse hooves, during the development of laminitis, a painful inflammation of this tissue.
- Fourteen Standardbred horses were given 10 g/kg bwt of oligofructose (a type of sugar) via a nasogastric tube, inducing laminitis. For each horse, one forelimb was continuously cooled in ice and water (the “CRYO” group), while the other forelimb was left at ambient temperature (the “NON-RX” group).
- Sampling of lamellae was done 24 hours post-oligofructose administration for the “DEV” group, whilst for the “OG1” group, lamellae were collected at the onset of lameness.
- From the sampled lamellae, mRNA was purified and cDNA produced for real-time quantitative PCR analysis. This was used to analyze the mRNA concentrations of various inflammatory mediators including cytokines, chemokines, cell adhesion molecules, and an enzyme called COX-2.
Results of the Study
- In the OG1 group, it was found that compared to the control group (CON), NON-RX horses had higher mRNA concentrations of all measured mediators, except for IL-10, IL-1β, and MCP-1/2. These mediators are associated with inflammation.
- It was also observed that within the OG1 group, CRYO limbs (compared with NON-RX) had decreased mRNA concentrations of the majority of measured inflammatory mediators, except for MCP-1 and IL-10. This suggests that digital hypothermia had an inhibitory effect on these inflammatory signals.
- In the DEV group, mRNA concentrations of certain inflammatory mediators were lower and the concentration of the anti-inflammatory cytokine IL-10 was higher in the CRYO limbs compared to the NON-RX limbs.
Conclusion
- According to the findings of the research, digital hypothermia effectively prevented early lamellar inflammatory activities which are likely to be crucial for lamellar injury.
- The study reveals a potential mechanism through which hypothermia can reduce the severity of acute laminitis, and it may help highlight molecular targets for future laminitis intervention.
Cite This Article
APA
van Eps AW, Leise BS, Watts M, Pollitt CC, Belknap JK.
(2011).
Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model.
Equine Vet J, 44(2), 230-237.
https://doi.org/10.1111/j.2042-3306.2011.00416.x Publication
Researcher Affiliations
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Queensland, Australia.
MeSH Terms
- Animals
- Cold Temperature
- Cytokines / genetics
- Cytokines / metabolism
- Female
- Foot Diseases / chemically induced
- Foot Diseases / physiopathology
- Foot Diseases / veterinary
- Gene Expression Regulation
- Hoof and Claw
- Horse Diseases / chemically induced
- Horse Diseases / physiopathology
- Horses
- Inflammation / chemically induced
- Inflammation / physiopathology
- Inflammation / veterinary
- Male
- Oligosaccharides / toxicity
- Real-Time Polymerase Chain Reaction
- Signal Transduction
Grant Funding
- UL1 TR000090 / NCATS NIH HHS
Citations
This article has been cited 14 times.- O' Brien C, Pegg J. A Preliminary Investigation into Ridden Water Submersion Training as an Adjunct to Current Condition Training Protocols in Performance Horses. Animals (Basel) 2021 Sep 7;11(9).
- Quam V, Yardley J, Quam M, Paz C, Belknap J. Cryotherapy provides transient analgesia in an induced lameness model in horses. Can Vet J 2021 Aug;62(8):834-838.
- Ding J, Li S, Jiang L, Li Y, Zhang X, Song Q, Hayat MA, Zhang JT, Wang H. Laminar Inflammation Responses in the Oligofructose Overload Induced Model of Bovine Laminitis. Front Vet Sci 2020;7:351.
- Stokes SM, Burns TA, Watts MR, Bertin FR, Stefanovski D, Medina-Torres CE, Belknap JK, van Eps AW. 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.
- Patan-Zugaj B, Egerbacher M, Licka TF. Endotoxin-induced changes in expression of cyclooxygenase isoforms in the lamellar tissue of extracorporeally haemoperfused equine limbs. Anat Histol Embryol 2020 Sep;49(5):597-605.
- Yang Q, Lopez MJ. Ultrastructural morphology is distinct among primary progenitor cell isolates from normal, inflamed, and cryopreserved equine hoof tissue and CD105(+)K14(+) progenitor cells. In Vitro Cell Dev Biol Anim 2019 Sep;55(8):641-655.
- Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils. Front Vet Sci 2019;6:69.
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- Morgan J, Stefanovski D, Lenfest M, Chatterjee S, Orsini J. Novel dry cryotherapy system for cooling the equine digit. Vet Rec Open 2018;5(1):e000244.
- Dern K, van Eps A, Wittum T, Watts M, Pollitt C, Belknap J. Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model. J Vet Intern Med 2018 Jan;32(1):450-458.
- Dern K, Watts M, Werle B, van Eps A, Pollitt C, Belknap J. Effect of Delayed Digital Hypothermia on Lamellar Inflammatory Signaling in the Oligofructose Laminitis Model. J Vet Intern Med 2017 Mar;31(2):575-581.
- Underberg BA, Van der Vekens E, Drews B, Kaessmeyer S. Cyclooxygenase-2 and von Willebrand factor-an immunohistochemical study of the equine foot with and without laminitis, post-mortem perfused with paraffin oil. Front Vet Sci 2025;12:1673415.
- Jacobs C, Schnabel LV, Redding Horne C, Tufts S, Martin EGM, Love K. Postoperative management following equine orthopedic surgery: a survey of diplomates of the ACVS and ACVSMR. Front Vet Sci 2025;12:1708401.
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