Effects of tumor necrosis factor blockade on interleukin 6, lactate, thromboxane, and prostacyclin responses in miniature horses given endotoxin.
Abstract: A monoclonal antibody (MAB) against equine tumor necrosis factor-alpha (Eq TNF) was used to investigate the role of TNF in cytokine, eicosanoid, and metabolic responses of Miniature Horses given endotoxin. Plasma concentrations of interleukin 6 (IL-6), lactate, thromboxane A2 metabolite, and prostacyclin metabolite (6-keto-PGF1 alpha) were measured in 10 Miniature Horses given 0.25 microgram of lipopolysaccharide (LPS; Escherichia coli O55:B5)/kg of body weight. Five horses were given Eq TNF MAB and 5 were given isotype-matched MAB as control. All horses were given 1.86 mg of antibody/kg by IV infusion, 5 minutes before LPS was given IV. Blood samples were taken 20 minutes before and at multiple intervals for 24 hours after LPS was given. Interleukin 6 bioactivity in plasma was measured, using IL-6-dependent cell line (B9). Eicosanoid activities were assessed by enzyme immunoassay, and plasma lactate concentration was determined enzymatically. Data were analyzed by ANOVA and Tukey's honest significant difference test for significant (P < 0.05) effect of treatment. Horses given Eq TNF MAB had significantly (P < 0.050) lower peak mean +/- SEM IL-6 (59 +/- 29 U/ml), lactate (16 +/- 2.00 mg/dl), and 6-keto-PGF1 alpha (254 +/- 79 pg/ml) values then did horses given control MAB (880 +/- 375 U/ml for IL-6; 26 +/- 0.04 mg/dl for lactate; and 985 +/- 290 pg/ml for 6-keto-PGF1 alpha). There was no effect of anti-TNF treatment on LPS-induced thromboxane A2 metabolite production. Tumor necrosis factor mediated IL-6, lactate, and prostacyclin responses, without affecting thromboxane production in horses given LPS.
Publication Date: 1995-11-01 PubMed ID: 8585654
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research article explores the effects of a monoclonal antibody for equine tumor necrosis factor-alpha on various molecular and metabolic responses in miniature horses injected with a bacterial endotoxin. The findings showed that horses treated with the antibody displayed significantly lower levels of interleukin 6, lactate, and prostacyclin metabolite after endotoxin administration, with no changes observed in thromboxane production.
Methodology
- The experiment involved ten Miniature Horses. Each horse was given a dose of lipopolysaccharide (LPS), an endotoxin derived from Escherichia coli O55:B5.
- The dosage of LPS given was proportional to the body weight of the horse, 0.25 microgram/kg.
- A monoclonal antibody (MAB) against equine tumor necrosis factor-alpha (EqTNF), a molecule involved in inflammatory pathways, was administered to half of the horses.
- The other half were given an isotype-matched MAB as a control. The antibody was administered intravenously five minutes before LPS injection.
- Blood samples were collected 20 minutes before and several times up to 24 hours after the LPS administration to measure the concentrations of various substances.
Measured Parameters
- Interleukin 6 (IL-6) bioactivity was measured with an IL-6 dependent cell line (B9). IL-6 is a cytokine, a type of protein that plays a crucial role in cell signaling during immune responses.
- Eicosanoid activities were evaluated by enzyme immunoassay. Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids that are similar to arachidonic acid.
- Plasma lactate concentration was also determined enzymatically. Lactate, the ionized form of lactic acid, often accumulates in blood as a result of oxygen depletion in tissues.
Results
- The horses treated with EqTNF MAB had significantly lower peak mean values for IL-6, lactate, and the prostacyclin metabolite 6-keto-PGF1 alpha. This suggests a possible role of TNF in mediating these responses.
- No differences in thromboxane A2 metabolite production, another eicosanoid, were observed between the treated and control group. This indicates the TNF blockade doesn’t affect this particular eicosanoid response.
Conclusion
- The researchers concluded that tumor necrosis factor mediates the production of IL-6, lactate, and prostacyclin responses in Miniature Horses given LPS but does not have an effect on thromboxane production. This research could facilitate the development of therapeutic strategies for managing inflammatory conditions in horses.
Cite This Article
APA
Cargile JL, MacKay RJ, Dankert JR, Skelley L.
(1995).
Effects of tumor necrosis factor blockade on interleukin 6, lactate, thromboxane, and prostacyclin responses in miniature horses given endotoxin.
Am J Vet Res, 56(11), 1445-1450.
Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0136, USA.
MeSH Terms
- 6-Ketoprostaglandin F1 alpha / blood
- Analysis of Variance
- Animals
- Antibodies, Monoclonal / pharmacology
- Endotoxins / pharmacology
- Escherichia coli
- Horses
- Interleukin-6 / blood
- Kinetics
- Lactates / blood
- Lipopolysaccharides / pharmacology
- Mice / immunology
- Thromboxane B2 / blood
- Time Factors
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / immunology
Citations
This article has been cited 3 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).
- Verma H, Rawat M, Verma R, Gandham R, Tiwari AK, Khan RIN, Praharaj MR, Smith E. First report of whole genome sequence of septicemic Pasteurella multocida serovar B:2 'Soron' strain isolated from swine. Braz J Microbiol 2023 Sep;54(3):2445-2460.
- Schmelzer KR, Kubala L, Newman JW, Kim IH, Eiserich JP, Hammock BD. Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc Natl Acad Sci U S A 2005 Jul 12;102(28):9772-7.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
