Correlation of clinical and laboratory data with serum tumor necrosis factor activity in horses with experimentally induced endotoxemia.
Abstract: Serum tumor necrosis factor (TNF) activity was quantitated in 8 horses given an IV infusion of endotoxin (0.03 micrograms of lipopolysaccharide/kg of body weight, from Escherichia coli 055:B5) in 0.9% NaCl solution over 1 hour. Serum TNF activity was likewise measured in 6 horses given only 0.9% sterile NaCl solution at the same rate. The duration of serum TNF activity was determined, and serum TNF activity was correlated with clinical and laboratory changes during the induced endotoxemia. Horses had no serum TNF activity prior to endotoxin administration, but geometric mean serum TNF activity was significantly higher from 1 to 4 hours after the start of the infusion. In response to endotoxin, horses seemed depressed, had signs of mild to moderate abdominal pain, developed tachycardia and fever, and had leukopenia followed by leukocytosis. Association between serum TNF activity and temperature, heart rate, attitude abnormality score, and WBC count of horses given endotoxin was significant. Serum TNF activity had a significant positive linear correlation with attitude abnormality and heart rate and a negative linear correlation with the WBC count during endotoxemia. Geometric mean serum TNF activity peaked approximately 1.5 hours prior to mean peak fever, and these data were significantly correlated. Results of this study suggest that TNF is an important mediator of endotoxemia in horses.
Publication Date: 1990-12-01 PubMed ID: 2085219
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research explored the relationship between the serum tumor necrosis factor (TNF) activity and the clinical and laboratory data in horses with endotoxemia, induced experimentally.
Experiment Design
- The experiment involved 8 horses given an intravenous infusion of endotoxin in a saline solution.
- A control group of 6 horses was given only sterile saline solution at the same rate.
- The endotoxin used was a small dose of lipopolysaccharide originating from Escherichia coli bacteria.
- No serum TNF activity was detected in these horses before the introduction of the endotoxin.
Observations and Outcomes
- Few hours after the start of the infusion, the level of serum TNF activity in horses given the endotoxin was significantly higher, showing a reaction to the injected endotoxin.
- The horses showed signs of depression, mild to moderate abdominal pain, increased heart rate, and a fever. These symptoms were followed by a decrease in white blood cell (WBC) count followed by an increase – a condition known as leukocytosis.
- There was a considerable association between the serum TNF activity and symptoms like temperature, heart rate, attitude changes, and white blood cell count in the horses given endotoxin.
Key Correlations
- The research found a significant positive linear correlation between the serum TNF activity and the attitude changes and heart rate in the horses.
- Conversely, there was a significant negative linear correlation between the serum TNF activity and the white blood cell count during the period of endotoxemia.
- Prior to the peak fever period, the mean TNF activity peaked approximately and these events were significantly correlated.
Conclusion
- The results of the study suggest that the tumor necrosis factor (TNF) plays a key role in mediating the effects of endotoxemia in horses.
Cite This Article
APA
Morris DD, Crowe N, Moore JN.
(1990).
Correlation of clinical and laboratory data with serum tumor necrosis factor activity in horses with experimentally induced endotoxemia.
Am J Vet Res, 51(12), 1935-1940.
Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
MeSH Terms
- Animals
- Endotoxins / administration & dosage
- Endotoxins / toxicity
- Escherichia coli Infections / blood
- Escherichia coli Infections / etiology
- Escherichia coli Infections / veterinary
- Female
- Horse Diseases / blood
- Horse Diseases / etiology
- Horses
- Infusions, Intravenous / veterinary
- Leukocytosis / etiology
- Leukocytosis / veterinary
- Male
- Neutropenia / etiology
- Neutropenia / veterinary
- Shock, Septic / blood
- Shock, Septic / etiology
- Shock, Septic / veterinary
- Time Factors
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 12 times.- 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).
- Bauquier J, Tudor E, Bailey S. Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses. J Vet Intern Med 2020 Sep;34(5):2109-2116.
- Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils. Front Vet Sci 2019;6:69.
- 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.
- Rütten S, Schusser GF, Abraham G, Schrödl W. Release kinetics of tumor necrosis factor-α and interleukin-1 receptor antagonist in the equine whole blood. BMC Vet Res 2016 Jun 17;12(1):117.
- Bonin CP, Baccarin RY, Nostell K, Nahum LA, Fossum C, de Camargo MM. Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites. Biochem Biophys Res Commun 2013 Mar 8;432(2):256-61.
- Coté N, Trout DR, Hayes AM. Evaluation of plasma alpha-2-macroglobulin and interactions with tumour necrosis factor-alpha in horses with endotoxemic signs. Can J Vet Res 1996 Apr;60(2):150-7.
- Morris DD, Crowe N, Moore JN. Reduced endotoxin-induced production of tumor necrosis factor activity by equine peritoneal macrophages exposed to the dual inhibitor of arachidonic acid metabolism, SK & F 86002. Can J Vet Res 1992 Apr;56(2):110-4.
- Urayama S, Muko R, Muranaka M, Mita H, Ohta M, Matsuda H, Tanaka A. Differential effects of flunixin meglumine and meloxicam on TNF- α production in LPS-stimulated equine neutrophils in vitro. Vet Anim Sci 2025 Dec;30:100513.
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