Disparate effects of LPS infusion and carbohydrate overload on inflammatory gene expression in equine laminae.
Abstract: Although clinical evidence of endotoxemia has been associated with the development of acute laminitis in hospitalized horses with gastrointestinal diseases and endotoxins have been detected in the circulation of horses with experimentally-induced laminitis, it is unclear what role, if any, endotoxins have play the pathogenesis of the disease. Therefore, in the present study we compared the effects of endotoxin infusion to that of intra-gastric administration of mixed carbohydrate (CHO) on clinical signs of laminitis, plasma concentrations of TNF-α and IL-10, and laminar tissue expression of 20 genes associated with inflammation. Horses were divided into 4 groups: Control (water placebo, n=7), endotoxin infusion (LPS, n=6), CHO/Developmental (30% decrease in central venous pressure, n=6) and CHO/Lame (Obel grade I laminitis, n=7). Horses in the LPS group developed clinical signs consistent with systemic inflammation, had rapid increases in plasma concentrations of both TNF-α and IL-10, and leukopenia, but did not have any changes in laminar tissue expression of the genes associated with inflammation. In contrast, horses administered CHO developed clinical signs consistent with systemic inflammation, had more delayed increases in TNF-α, IL-10 and total leukocyte counts, and had marked increases in laminar tissue expression of the genes associated with inflammation. Only the horses administered CHO developed clinical signs of laminitis, providing additional credence to the concept that factors other than endotoxin are responsible for the changes in laminar tissue gene expression that occur during the development of acute equine laminitis.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication Date: 2013-06-10 PubMed ID: 23820116DOI: 10.1016/j.vetimm.2013.05.001Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the difference in inflammatory responses in horses caused by both carbohydrate overload and Lipopolysaccharides (LPS) infusion to better understand their role in the development of acute laminitis, a common and debilitating disease in horses.
Objective and Approach
- The main purpose of this study was to determine the involvement of endotoxins, such as Lipopolysaccharides (LPS), in the development of acute laminitis and their influence on the genes associated with inflammation.
- The researchers administrated either mixed carbohydrates (CHO) or LPS endotoxin directly to the horses and then compared the variations in clinical signs of laminitis, levels of plasma TNF-α (Tumor necrosis factor alpha) and IL-10 (Interleukin 10), and the impact on laminar tissue genes linked with inflammation.
Experiment and Findings
- The horses were classified into four groups: The control group received a water placebo, one group received the LPS endotoxin, and the remaining two groups were given CHO. One of the CHO group’s venous pressure was lowered by 30%, while the other was made to develop Obel grade I laminitis.
- The results showed that horses given LPS developed symptoms consistent with systemic inflammation— they displayed rapid increments in the levels of TNF-α and IL-10 and leukopenia (reduction in white blood cells). However, there were no changes observed in the laminar tissue genes involved with inflammation.
- On the other hand, the CHO-administered horses also showed signs of systemic inflammation but at a much slower pace, including increased TNF-α, IL-10, and total white blood cell counts. More importantly, these horses showed a significant increase in the expression of genes associated with inflammation in the laminar tissues and also displayed clinical signs of laminitis.
Conclusion
- These findings suggest that factors other than endotoxins might be responsible for the onset of acute equine laminitis. Inflammation changes in laminar tissue genes appear to be more associated with carbohydrates than LPS.
- Thus, the study provides additional validation to the idea that in the pathogenesis of acute laminitis, excessive carbohydrate consumption plays a more crucial role than endotoxins like LPS.
Cite This Article
APA
Kwon S, Moore JN, Robertson TP, Hurley DJ, Wagner B, Vandenplas ML.
(2013).
Disparate effects of LPS infusion and carbohydrate overload on inflammatory gene expression in equine laminae.
Vet Immunol Immunopathol, 155(1-2), 1-8.
https://doi.org/10.1016/j.vetimm.2013.05.001 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
MeSH Terms
- Animals
- Dietary Carbohydrates / administration & dosage
- Endotoxemia / genetics
- Endotoxemia / immunology
- Endotoxemia / veterinary
- Female
- Foot Diseases / genetics
- Foot Diseases / immunology
- Foot Diseases / veterinary
- Gene Expression / drug effects
- Hoof and Claw
- Horse Diseases / etiology
- Horse Diseases / genetics
- Horse Diseases / immunology
- Horses / genetics
- Horses / immunology
- Inflammation / genetics
- Inflammation / immunology
- Inflammation / veterinary
- Interleukin-10 / blood
- Lameness, Animal / etiology
- Lameness, Animal / genetics
- Lameness, Animal / immunology
- Lipopolysaccharides / administration & dosage
- Male
- Tumor Necrosis Factor-alpha / blood
Citations
This article has been cited 7 times.- Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A. Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys. J Vet Intern Med 2020 Jul;34(4):1631-1641.
- Taylor S. A review of equine sepsis. Equine Vet Educ 2015 Feb;27(2):99-109.
- Tian MY, Fan JH, Zhuang ZW, Dai F, Wang CY, Hou HT, Ma YZ. Effects of silymarin on p65 NF-κB, p38 MAPK and CYP450 in LPS-induced hoof dermal inflammatory cells of dairy cows. BMC Vet Res 2019 Apr 30;15(1):127.
- Martin EM, Schirmer JM, Jones SL, Davis JL. Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses. Equine Vet J 2019 May;51(3):415-421.
- Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes. Front Vet Sci 2017;4:160.
- Holl HM, Gao S, Fei Z, Andrews C, Brooks SA. Generation of a de novo transcriptome from equine lamellar tissue. BMC Genomics 2015 Oct 3;16:739.
- Lan X, Qi D, Ren H, Liu T, Shao H, Zhang J. Chicoric acid ameliorates LPS-induced inflammatory injury in bovine lamellar keratinocytes by modulating the TLR4/MAPK/NF-κB signaling pathway. Sci Rep 2023 Dec 11;13(1):21963.
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