Modulation of TNF-α, IL-1Ra and IFN-γ in equine whole blood culture by glucocorticoids.
Abstract: Glucocorticoids are important drugs in the treatment of many inflammatory, autoimmune and allergic diseases in humans and animals. We investigated the effects of hydrocortisone and dexamethasone on TNF-α, IL-1Ra and INF-γ release in stimulated whole blood cell culture from healthy horses. Whole blood cell cultures proved to be useful for the characterization of the anti-inflammatory properties of new drugs. Diluted equine whole blood was exposed to lipopolysaccharide (LPS) and PCPwL (a cocktail consisting of phythemagglutinin E, concanavalin A, pokeweed mitogen and lipopolysaccharide) in the presence or absence of hydrocortisone and dexamethasone (10 - 10 M). TNF-α and IL-1Ra (LPS) as well as IFN-γ (PCPwL) levels were measured in the supernatants using specific enzyme-linked immunosorbent assay (ELISA). The LPS-induced TNF-α and IL-1Ra as well as the PCPwL-induced IFN-γ levels were more potently suppressed by dexamethasone than by hydrocortisone in a concentration-dependent manner. Dexamethasone inhibited TNF-α, IL-1Ra and IFN-γ with the half maximal inhibition concentration (IC) values of 0.09 μM, 0.453 μM and 0.001 μM, respectively, whereas hydrocortisone inhibited these cytokines with lower IC values of 1.45 μM, 2.96 μM and 0.09 μM, respectively. Our results suggest that the equine whole blood test system is useful and reliable to evaluate drug effects and immunological alterations and offers several advantages including simple and cheap performance in physiological and pathological conditions.
Copyright © 2019 Elsevier B.V. All rights reserved.
Publication Date: 2019-03-04 PubMed ID: 30947974DOI: 10.1016/j.vetimm.2019.03.002Google Scholar: Lookup
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Summary
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This research explored the effects of glucocorticoids, specifically hydrocortisone and dexamethasone, on the release of certain immune system factors (TNF-α, IL-1Ra, and IFN-γ) in horse blood cultures. The study findings indicate that dexamethasone more successfully suppressed these immune factors than hydrocortisone.
Research Context and Objectives
- The research focuses on glucocorticoids, drugs widely used to treat various inflammatory, autoimmune, and allergic diseases in humans and animals.
- Focusing on the effects of two specific glucocorticoids—hydrocortisone and dexamethasone—the investigators aimed to measure their effects on the release of certain immune factors in the blood. The immune factors studied were TNF-α, IL-1Ra, and IFN-γ.
- The study isolated these factors from blood cell cultures of healthy horses, testing the applicability of this method for new drug evaluation.
Methodology
- The investigators stimulated the horse’s whole blood cells with lipopolysaccharide (LPS) and a cocktail called PCPwL, which included different immune system stimulators.
- The cultures were exposed to these stimulants in the presence or absence of hydrocortisone and dexamethasone in specified concentrations.
- Following stimulation, the levels of TNF-α and IL-1Ra (induced by LPS), as well as IFN-γ (induced by PCPwL), were measured in the supernatant (fluid part of the culture) using an enzyme-linked immunosorbent assay (ELISA).
Results and Significance
- The researchers found that dexamethasone was more potent in suppressing the immune factors TNF-α, IL-1Ra, and IFN-γ than hydrocortisone.
- The measure of drug effectiveness, the half maximal inhibition concentration (IC), was lower for dexamethasone than for hydrocortisone, showing dexamethasone’s stronger inhibitory effect.
- Finally, the study highlighted the practicality of the equine whole blood test system in assessing drug effects and immunological changes, offering a simple and cost-effective option for drug evaluation in both physiological and pathological conditions.
Cite This Article
APA
Rütten S, Schrödl W, Abraham G.
(2019).
Modulation of TNF-α, IL-1Ra and IFN-γ in equine whole blood culture by glucocorticoids.
Vet Immunol Immunopathol, 210, 1-5.
https://doi.org/10.1016/j.vetimm.2019.03.002 Publication
Researcher Affiliations
- Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, An den Tierkliniken 15, 04103 Leipzig, Germany.
- Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, An den Tierkliniken 15, 04103 Leipzig, Germany; Institute of Bacteriology und Mycology, University of Leipzig, 04103 Leipzig, Germany.
- Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, An den Tierkliniken 15, 04103 Leipzig, Germany. Electronic address: gabraham@rz.uni-leipzig.de.
MeSH Terms
- Animals
- Blood / drug effects
- Cells, Cultured
- Concanavalin A / pharmacology
- Dexamethasone / pharmacology
- Glucocorticoids / pharmacology
- Horses
- Hydrocortisone / pharmacology
- Inhibitory Concentration 50
- Interferon-gamma / antagonists & inhibitors
- Interferon-gamma / blood
- Lipopolysaccharides / pharmacology
- Receptors, Interleukin-1 / antagonists & inhibitors
- Receptors, Interleukin-1 / blood
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / blood
Citations
This article has been cited 4 times.- Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review. J Vet Intern Med 2021 Jul;35(4):2045-2057.
- Peng X, Wang Y, Xi X, Jia Y, Tian J, Yu B, Tian J. Promising Therapy for Heart Failure in Patients with Severe COVID-19: Calming the Cytokine Storm. Cardiovasc Drugs Ther 2021 Apr;35(2):231-247.
- 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).
- 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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