Effect of tumor necrosis factor antibody given to horses during early experimentally induced endotoxemia.
Abstract: To test efficacy of murine monoclonal, rabbit polyclonal recombinant equine or human tumor necrosis factor-alpha (rETNF or rHTNF, respectively) antibodies to inhibit native equine tumor necrosis factor (TNF) activity. Methods: 8 and 18 healthy adult horses for parts 1 and 2 of the study, respectively. Methods: In part 1, supernates from endotoxin-activated peritoneal macrophages were incubated with various dilutions of each rETNF antibody and subsequently tested for TNF activity. Serum was also obtained from a horse 1 hour after infusion with 20 ng of endotoxin/kg of body weight and was incubated with various dilutions of rabbit polyclonal rHTNF antibody. In part 2, 20 ng of endotoxin/kg was infused in horses during a 30-minute period. Fifteen minutes after the endotoxin infusion was initiated, 1 of 3 preparations was infused: 0.1 mg of rabbit polyclonal (rHTNF antibody/kg, 0.1 mg of human IgG/kg, or 500 ml of 5% dextrose. Clinical and hematologic data were collected for 24 hours. Results: Compared with the monoclonal antibody, the rabbit polyclonal rETNF antibody was more effective in inhibiting TNF activity. The 50% effective doses of the murine monoclonal rETNF, rabbit polyclonal rETNF, and rabbit rHTNF antibodies were 1.8, 0.8, and 0.6 micrograms of antibody/ml, respectively. In part 2, endotoxin infusion resulted in significant alternations in all variables; however, differences among treatment groups were not significant. Conclusions: Although murine monoclonal and rabbit polyclonal rETNF or rHTNF antibodies are capable of inhibiting native equine TNF activity in vitro, when given after initiation of endotoxemia, administration of 0.1 mg of rabbit polyclonal rHTNF/kg does not alter the response to infusion of endotoxin.
Publication Date: 1998-06-12 PubMed ID: 9622754
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research examines the effectiveness of various antibodies in inhibiting the activity of a protein called ‘tumor necrosis factor’ during early stages of endotoxemia in horses, a condition triggered by toxins found in bacteria, with the conclusion that while certain antibodies can inhibit the protein in laboratory settings, administering these antibodies does not change the response to an endotoxin infusion.
Objective and Methodology
- The primary aim of the research study was to analyze the effectiveness of four variations of tumor necrosis factor-alpha (TNF-alpha) antibodies in curbing the activity of the natural TNF in horses.
- The study was conducted in two separate parts, involving different numbers of adult horses (8 in part 1, 18 in part 2).
- First, supernates from endotoxin-activated macrophages were exposed to different concentrations of each antibody, followed by tests for TNF activity. Serum was also obtained from a horse after endotoxin infusion and exposed to various concentrations of a specific antibody.
- In the second part, the horses were infused with endotoxin while simultaneously being exposed to one of three other substances, followed by collection of clinical and hematologic data for 24 hours.
Results
- The results indicated that compared to a monoclonal antibody, the rabbit polyclonal rETNF antibody was more effective in inhibiting TNF activity.
- The effective doses for TNF activity inhibition were different across the types of antibodies, being highest for murine monoclonal rETNF antibody and lowest for rabbit rHTNF antibodies.
- While the effect of endotoxin infusion was significant on all variables, the differences between the different treatment groups weren’t significant.
Conclusion
- The researchers concluded that although certain types of antibodies – i.e., the murine monoclonal and the rabbit polyclonal rETNF or rHTNF antibodies – are capable of inhibiting the natural TNF activity in vitro, administering these antibodies after the onset of endotoxemia does not change the response to endotoxin infusion.
- This suggests the antibodies may not be as effective as previously thought in mitigating the effects of endotoxemia in horses.
Cite This Article
APA
Barton MH, Bruce EH, Moore JN, Norton N, Anders B, Morris DD.
(1998).
Effect of tumor necrosis factor antibody given to horses during early experimentally induced endotoxemia.
Am J Vet Res, 59(6), 792-797.
Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30628, USA.
MeSH Terms
- Animals
- Antibodies / therapeutic use
- Antibodies, Monoclonal / therapeutic use
- Endotoxemia / immunology
- Endotoxemia / therapy
- Endotoxemia / veterinary
- Endotoxins / toxicity
- Horse Diseases / immunology
- Horse Diseases / therapy
- Horses
- Humans
- Macrophages, Peritoneal / drug effects
- Macrophages, Peritoneal / immunology
- Mice
- Rabbits
- Recombinant Proteins / therapeutic use
- Tumor Necrosis Factor-alpha / immunology
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 3 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.
- 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.
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