Effect of treatment with a monoclonal antibody against equine tumor necrosis factor (TNF) on clinical, hematologic, and circulating TNF responses of miniature horses given endotoxin.
Abstract: Tumor necrosis factor-alpha (TNF) is an important mediator of endotoxin-induced pathologic changes. To help define the role of TNF in equids with endotoxemia, the effects of pretreatment with a murine monoclonal antibody (MAB) against equine TNF were evaluated in Miniature Horses given endotoxin. Five horses were given TNF MAB at a dosage of 1.86 mg/kg of body weight, IV, and 5 were given control MAB. Five minutes later, lipopolysaccharide (LPS; Escherichia coli O55:B5), 0.25 microgram/kg, was given to all horses by bolus IV infusion. Clinical signs of disease were monitored at intervals up to 24 hours after LPS infusion, and blood was taken for determination of WBC count, PCV, plasma total protein concentration, plasma TNF activity, and serum MAB concentration. Reduction of plasma TNF activity in anti-TNF-treated horses was highly significant (P < 0.001), compared with that in control horses. Horses given TNF MAB had significantly improved clinical abnormality score (P < 0.010), lower heart rate (P < 0.001), and higher WBC count (P < 0.001), compared with horses given control MAB. Rectal temperature, respiratory rate, PCV, and plasma total protein concentration were not significantly different between groups. Serum MAB concentration peaked at 68 micrograms/ml 30 minutes after the end of antibody infusion in both groups. Neutralization of LPS-induced TNF activity reduced the hematologic and clinical responses of horses given LPS IV.
Publication Date: 1995-11-01 PubMed ID: 8585655
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- Clinical Trial
- Comparative Study
- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research paper investigates the effect of treating miniature horses with a certain antibody to counteract the potentially harmful effects of endotoxins. The results show that the use of this treatment significantly lessened the clinical and blood-related responses in the horses.
Methodology of Study
- The researchers used 10 miniature horses for their study. Five of these were given the monoclonal antibody (MAB) specifically designed to combat the equine TNF, a harmful mediator triggered by endotoxin introduction, at a dosage ratio of 1.86 mg/kg of body weight. The other five were given a control MAB.
- Five minutes after the antibody was administered, all horses were given a bolus infusion of lipopolysaccharide (LPS; Escherichia coli O55:B5), a type of harmful endotoxin, at a concentration of 0.25 micrograms per kg of body weight.
- The horses were then monitored over the next 24 hours for clinical signs of disease. In addition, blood tests were conducted to check for white blood cell (WBC) count, packed cell volume (PCV), total plasma protein concentration, plasma TNF activity, and serum MAB concentration.
Results of the Study
- The treatment proved highly effective in reducing plasma TNF activity in the horses given the TNF MAB. The reduction was deemed highly significant in comparison to the control group horses.
- It was also noticed that horses treated with the TNF MAB displayed a significantly better clinical abnormality score, indicating improved health conditions. They also had a lower heart rate and a higher WBC count than those given control MAB.
- No significant difference was found between the two groups in terms of rectal temperature, respiratory rate, PCV, and plasma total protein concentration.
- Peak serum MAB concentration was observed 30 minutes after the ending of antibody infusion, at 68 micrograms per ml, in both groups.
Conclusion of the Study
- The study concluded that the neutralization of the harmful LPS-induced TNF activity considerably depreciated the blood-related and clinical responses in horses when given endotoxins intravenously.
- This suggests that the use of a monoclonal antibody for TNF can significantly mitigate the harmful effects of endotoxins in miniature horses, providing a potential treatment mechanism.
Cite This Article
APA
Cargile JL, MacKay RJ, Dankert JR, Skelley L.
(1995).
Effect of treatment with a monoclonal antibody against equine tumor necrosis factor (TNF) on clinical, hematologic, and circulating TNF responses of miniature horses given endotoxin.
Am J Vet Res, 56(11), 1451-1459.
Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0136, USA.
MeSH Terms
- Analysis of Variance
- Animals
- Antibodies, Monoclonal / pharmacology
- Blood Proteins / drug effects
- Blood Proteins / metabolism
- Body Temperature / drug effects
- Endotoxins / pharmacology
- Escherichia coli
- Female
- Heart Rate / drug effects
- Horses
- Immunoglobulin G / blood
- Kinetics
- Leukocyte Count / drug effects
- Lipopolysaccharides / pharmacology
- Male
- Mice
- Respiration / drug effects
- Time Factors
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / immunology
- Tumor Necrosis Factor-alpha / metabolism
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