Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses.
Abstract: To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis. Methods: 12 healthy adult horses (10 mares and 2 geldings). Methods: Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammatory cytokine gene expression was determined for blood samples obtained every 8 hours, and IV glucose tolerance tests were performed. Results: All LPS-treated horses had signs of depression and mild colic; those signs abated as the study progressed. Administration of LPS increased expression of interleukin-1β, interleukin-6, and interleukin-8, but results were not significantly different between LPS treatment groups. Cytokine expression was significantly higher on the first day versus the second day of LPS treatment. Interleukin-1β expression was positively correlated with rectal temperature and expression of other cytokines. Glucose and insulin dynamics for both LPS groups combined did not differ significantly from those of the saline solution group. Signs of laminitis were not detected in any of the horses. Conclusions: Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.
Publication Date: 2012-08-29 PubMed ID: 22924721DOI: 10.2460/ajvr.73.9.1394Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research is about the impacts of administering lipopolysaccharide (LPS), either intermittently or continuously for 48 hours, on the systemic inflammatory response in horses. It found that repetitive LPS exposure led to the development of tolerance within 24 hours, irrespective of the mode of administration, and did not induce laminitis.
Objective of the Study
- The primary aim of this study was to investigate how the two modes of lipopolysaccharide (LPS) administration (continuous vs intermittent) affect the intensity and duration of the systemic inflammatory response in horses.
- The study had a secondary goal to test whether prolonged endotoxemia (endotoxic shock) for 48 hours could trigger the development of laminitis, a painful and potentially crippling hoof disorder, in horses.
Methodology
- The study involved twelve healthy adult horses (10 mares and 2 geldings).
- The horses were randomly assigned to receive either an LPS (a total dose of 80 μg) or a saline solution as constant rate infusions or eight bolus IV injections over a 48-hour period.
- Every four hours, horses underwent physical examinations, while inflammatory cytokine gene expression tests were carried out through blood samples collected every eight hours.
- Additionally, Intravenous Glucose Tolerance Tests (IV GTT) were performed to check glucose and insulin dynamics.
Results
- All LPS-treated horses exhibited signs of depression and mild colic, though these symptoms subsided as the study continued.
- The administration of LPS resulted in increased expression of immune response proteins interleukin-1β, interleukin-6, and interleukin-8. However, the mode of LPS administration did not significantly influence these results.
- The expression of cytokines was significantly higher on the first day of LPS application than the second day, indicative of the development of LPS tolerance.
- No significant deviation was found in glucose and insulin dynamics between both LPS groups and the saline solution group.
- No signs of laminitis were observed in any of the horses.
Conclusion
- The study revealed that horses developed LPS tolerance within approximately 24 hours of administration, irrespective of the mode of LPS delivery.
- Furthermore, the method of LPS delivery did not significantly affect the duration or intensity of systemic inflammation.
- Laminitis was not observed in horses as a result of prolonged endotoxemia.
Cite This Article
APA
Tadros EM, Frank N.
(2012).
Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses.
Am J Vet Res, 73(9), 1394-1402.
https://doi.org/10.2460/ajvr.73.9.1394 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
MeSH Terms
- Animals
- Area Under Curve
- Blood Glucose / metabolism
- Endotoxemia / blood
- Endotoxemia / chemically induced
- Endotoxemia / immunology
- Endotoxemia / veterinary
- Female
- Foot Diseases / blood
- Foot Diseases / chemically induced
- Foot Diseases / immunology
- Foot Diseases / veterinary
- Glucose Tolerance Test / veterinary
- Horse Diseases / blood
- Horse Diseases / chemically induced
- Horse Diseases / immunology
- Horses
- Inflammation / blood
- Inflammation / chemically induced
- Inflammation / immunology
- Inflammation / veterinary
- Insulin / blood
- Interleukin-1beta / blood
- Interleukin-6 / blood
- Interleukin-8 / blood
- Lipopolysaccharides / administration & dosage
- Lipopolysaccharides / immunology
- Male
- Random Allocation
Citations
This article has been cited 14 times.- Hobbs KJ, Bayless R, Sheats MK. A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses. Cells 2024 Sep 5;13(17).
- Mercer MA, Davis JL, McKenzie HC. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses. Animals (Basel) 2023 May 10;13(10).
- Mukhopadhyay A, Cook SR, SanMiguel P, Ekenstedt KJ, Taylor SD. TLR4 and MD2 variation among horses with differential TNFα baseline concentrations and response to intravenous lipopolysaccharide infusion. Sci Rep 2023 Jan 27;13(1):1486.
- Gugliandolo E, Crupi R, Biondi V, Licata P, Cuzzocrea S, Passantino A. Protective Effect of Silibinin on Lipopolysaccharide-Induced Inflammatory Responses in Equine Peripheral Blood Mononuclear Cells, an In Vitro Study. Animals (Basel) 2020 Nov 3;10(11).
- Scavone D, Sgorbini M, Borges AS, Oliveira-Filho JP, Vitale V, Paltrinieri S. Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia. BMC Vet Res 2020 Nov 4;16(1):422.
- 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.
- Starzonek J, Roscher K, Blüher M, Blaue D, Schedlbauer C, Hirz M, Raila J, Vervuert I. Effects of a blend of green tea and curcuma extract supplementation on lipopolysaccharide-induced inflammation in horses and ponies. PeerJ 2019;7:e8053.
- Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils. Front Vet Sci 2019;6:69.
- 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.
- Andreassen SM, Vinther AML, Nielsen SS, Andersen PH, Tnibar A, Kristensen AT, Jacobsen S. Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses. BMC Vet Res 2017 Jun 19;13(1):182.
- Vinther AM, Heegaard PM, Skovgaard K, Buhl R, Andreassen SM, Andersen PH. Characterization and differentiation of equine experimental local and early systemic inflammation by expression responses of inflammation-related genes in peripheral blood leukocytes. BMC Vet Res 2016 Jun 1;12:83.
- Bauquier JR, Forbes G, Nath L, Tudor E, Bailey SR. Plasma HMGB-1 and Nucleosome Concentrations in Horses with Colic and Healthy Horses. J Vet Intern Med 2016 Jan-Feb;30(1):260-8.
- Vinther AM, Skovgaard K, Heegaard PM, Andersen PH. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation. BMC Vet Res 2015 Jun 16;11:134.
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