Induction of the acute-phase cytokine, hepatocyte-stimulating factor/interleukin 6, in the circulation of horses treated with endotoxin.
Abstract: Because hepatocyte-stimulating factor/interleukin 6 (IL-6) is the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating IL-6 activity was monitored in 4 adult horses for 72 hours after IV administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin--1,000 30, 1, and 0 ng/kg of body weight. Plasma IL-6 activity was quantified as the ability to promote growth of the IL-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 +/- 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P less than 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kgt dosage of endotoxin, peak plasma IL-6 activity (10,128 +/- 4,096 and 1,555 +/- 1,326 U/ml, respectively) was observed for 3 hours. The IL-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma IL-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer.
Publication Date: 1992-08-01 PubMed ID: 1510298
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- Journal Article
Summary
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The research is about an experiment on horses to measure the increase in interleukin 6, a protein associated with inflammation, in response to treatment with different doses of endotoxin. This experiment is aimed at quantifying the onset of the body’s acute-phase response.
Summary of the Research
- The researchers carried out an experiment on four adult horses, where they introduced varying amounts of endotoxin into their systems intravenously, then monitored the levels of interleukin 6 (IL-6) – a cytokine activated during inflammation – in the horses’ blood for a period of 72 hours.
- Four different doses of endotoxin were used – 1,000 ng/kg, 30 ng/kg, 1 ng/kg, and 0 ng/kg, where the last one served as a control. Experiments were conducted on a weekly basis and in a randomized order.
Quantifying IL-6 Activity
- The researchers quantified the activity of IL-6 by assessing its ability to promote the proliferation of a specific B-cell hybridoma called B13.29 clone B9.
- Significant IL-6 activity was detected in all pre-treatment plasma samples.
Key Findings
- 2 to 12 hours after administering 1000 ng/kg of endotoxin, and 3 hours after giving 30 ng/kg of endotoxin, the horses showed significantly increased IL-6 activity above baseline levels.
- The peak plasma IL-6 activity was observed at 3 hours post endotoxin administration for both the 1000 ng/kg and 30 ng/kg endotoxin doses. The observed peak values were over 10,000 U/ml and 1,500 U/ml respectively.
- Horses that received the lowest dose of endotoxin (1 ng/kg) or the control buffer did not exhibit any significant increase in IL-6 activity.
- An increase in IL-6 activity in response to endotoxin treatment started approximately 1 hour after the appearance of tumor necrosis factor (another cytokine involved in systemic inflammation) in the blood. According to the researchers, this observed course mirrors the endotoxin-induced fever response.
Conclusion
- The data can be interpreted to suggest that endotoxin exposure in horses leads to a measurable and dose-dependent increase in IL-6 activity, indicative of an induced acute-phase inflammatory response.
Cite This Article
APA
MacKay RJ, Lester GD.
(1992).
Induction of the acute-phase cytokine, hepatocyte-stimulating factor/interleukin 6, in the circulation of horses treated with endotoxin.
Am J Vet Res, 53(8), 1285-1289.
Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610.
MeSH Terms
- Acute-Phase Reaction / blood
- Acute-Phase Reaction / veterinary
- Animals
- Body Temperature / drug effects
- Endotoxins / pharmacology
- Escherichia coli
- Heart Rate / drug effects
- Horse Diseases / blood
- Horses
- Interleukin-6 / biosynthesis
- Interleukin-6 / blood
- Leukocyte Count / drug effects
- Leukocyte Count / veterinary
- Lipopolysaccharides / toxicity
- Male
- Tumor Necrosis Factor-alpha / analysis
Citations
This article has been cited 7 times.- Taylor SD, Serpa PBS, Santos AP, Hart KA, Vaughn SA, Moore GE, Mukhopadhyay A, Page AE. Effects of intravenous administration of peripheral blood-derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses. J Vet Intern Med 2022 Jul;36(4):1491-1501.
- Anderson MJ, Ibrahim AS, Cooper BR, Woolcock AD, Moore GE, Taylor SD. Effects of administration of ascorbic acid and low-dose hydrocortisone after infusion of sublethal doses of lipopolysaccharide to horses. J Vet Intern Med 2020 Nov;34(6):2710-2718.
- Taylor S. A review of equine sepsis. Equine Vet Educ 2015 Feb;27(2):99-109.
- Cheng G, Zhao Y, Li H, Wu Y, Li X, Han Q, Dai C, Li Y. Forsythiaside attenuates lipopolysaccharide-induced inflammatory responses in the bursa of Fabricius of chickens by downregulating the NF-κB signaling pathway. Exp Ther Med 2014 Jan;7(1):179-184.
- Lewis DH, Chan DL, Pinheiro D, Armitage-Chan E, Garden OA. The immunopathology of sepsis: pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T cells. J Vet Intern Med 2012 May-Jun;26(3):457-82.
- Hubert JD, Seahorn TL, Klei TR, Hosgood G, Horohov DW, Moore RM. Clinical signs and hematologic, cytokine, and plasma nitric oxide alterations in response to Strongylus vulgaris infection in helminth-naïve ponies. Can J Vet Res 2004 Jul;68(3):193-200.
- Sousa LN, Winter IC, Varela DD, Luvison EZ, Guzmán JFC, Machado AMV, Figueiredo RDV, Pena GT, Dos Santos ACS, Faleiros RR, Carvalho AM. Lidocaine's Ineffectiveness in Mitigating Lipopolysaccharide-Induced Pain and Peristaltic Effects in Horses. Animals (Basel) 2024 Nov 2;14(21).
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