Can levamisole upregulate the equine cell-mediated macrophage (M1) dendritic cell (DC1) T-helper 1 (CD4 Th1) T-cytotoxic (CD8) immune response in vitro?
Abstract: Equine protozoal myeloencephalitis (EPM) is a common and devastating neurologic disease of horses in the United States. Because some EPM-affected horses have decreased immune responses, immunomodulators such as levamisole have been proposed as supplemental treatments. However, little is known about levamisole's effects or its mechanism of action in horses. Objective: Levamisole in combination with another mitogen will stimulate a macrophage 1 (M1), dendritic cell 1 (DC1), T-helper 1 (CD4 Th1), and T-cytotoxic (CD8) immune response in equine peripheral blood mononuclear cells (PBMCs) in vitro as compared to mitogen alone. Methods: Ten neurologically normal adult horses serologically negative for Sarcocystis neurona. Methods: Prospective study. Optimal conditions for levamisole were determined based on cellular proliferation. Peripheral blood mononuclear cells were then cultured using optimal conditions of mitogen and levamisole to identify the immune phenotype, based on subset-specific activation markers, intracellular cytokine production, and cytokine concentrations in cell supernatants. Subset-specific proliferation was determined using a vital stain. Results: Concanavalin A (conA) with levamisole, but not levamisole alone, resulted in a significant decrease (P < .05) in PBMC proliferation compared to conA alone. Levamisole alone did not elicit a specific immune phenotype different than that induced by conA. Conclusions: Levamisole co-cultured with conA significantly attenuated the PBMC proliferative response as compared with conA. If the mechanisms by which levamisole modulates the immune phenotype can be further defined, levamisole may have potential use in the treatment of inflammatory diseases.
© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Publication Date: 2019-01-29 PubMed ID: 30693587PubMed Central: PMC6430894DOI: 10.1111/jvim.15404Google Scholar: Lookup
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- Journal Article
- Cell Proliferation
- Cytokines
- Dendritic Cells
- Disease Treatment
- Equine Health
- Equine Protozoal Myeloencephalitis
- Immune Response
- Immunology
- In Vitro Research
- Inflammatory Response
- Macrophages
- Mononuclear Cells
- Neurological Diseases
- Pharmacology
- Sarcocystis
- Veterinary Care
- Veterinary Medicine
- Veterinary Research
- White Blood Cells
Summary
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The abstract presents a research on the potential use of levamisole to stimulate certain equine immune responses, specifically targeting the macrophage 1, dendritic cell 1, T-helper 1, and T-cytotoxic immune response. The research is motivated by the desire to explore treatments for equine protozoal myeloencephalitis, a common and destructive neurological disease affecting horses.
Objective of the study
- The study intended to analyze if levamisole, in combination with another mitogen, could invigorate a range of specified immune responses in equine peripheral blood mononuclear cells. The immune responses aimed at were for macrophage 1, dendritic cell 1, T-helper 1, and T-cytotoxic.
Methods
- The study was carried out prospectively using ten adult horses, all neurologically stable and showing no serological indications of Sarcocystis neurona.
- The research initially sought optimal conditions for the use of levamisole via monitoring cellular proliferation under varying conditions.
- The peripheral blood mononuclear cells were cultured under these selected conditions with levamisole and a mitogen, and the resultant immune phenotype was identified using a variety of indicators like subset-specific activation markers, cytokine concentrations in cell supernatants, and intracellular cytokine production.
- The study then determined subset-specific proliferation using a vital stain.
Results
- The co-culture of levamisole with Concanavalin A (ConA), another mitogen, resulted in a significant decrease in PBMC proliferation compared to ConA alone. This means that levamisole can modulate the response of these cells, influencing their proliferation.
- Levamisole alone, however, did not elicit a distinct immune phenotype dissimilar to that induced by ConA.
Conclusions
- The study concludes that levamisole can affect the proliferative response of PBMCs when co-cultured with ConA.
- The exact mechanisms by which levamisole manipulates this immune phenotype need further exploration. If understood thoroughly, levamisole might become a potential treatment option for inflammatory diseases.
Cite This Article
APA
Witonsky S, Buechner-Maxwell V, Santonastasto A, Pleasant R, Werre S, Wagner B, Ellison S, Lindsay D.
(2019).
Can levamisole upregulate the equine cell-mediated macrophage (M1) dendritic cell (DC1) T-helper 1 (CD4 Th1) T-cytotoxic (CD8) immune response in vitro?
J Vet Intern Med, 33(2), 889-896.
https://doi.org/10.1111/jvim.15404 Publication
Researcher Affiliations
- Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
- Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
- Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
- Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
- Study Design and Statistical Analysis Lab, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
- Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY.
- Pathogenes, Inc, Fairfield, FL.
- Biomedical Sciences and Pathobiology, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
MeSH Terms
- Adjuvants, Immunologic / pharmacology
- Animals
- Cells, Cultured
- Concanavalin A / pharmacology
- Female
- Horses / immunology
- Leukocytes, Mononuclear / drug effects
- Leukocytes, Mononuclear / immunology
- Levamisole / pharmacology
- Male
- Mitogens / pharmacology
- Prospective Studies
- Up-Regulation
Grant Funding
- 441087 / Veterinary Memorial Fund
- 449264 / Virginia Horse Industry Board
- American College of Veterinary Internal Medicine
Conflict of Interest Statement
Dr. Ellison owns Pathogenes and sells levamisole alone or in combination with decoquinate as treatment for equine protozoal myeloencephalitis. Pathogenes performed the IL‐6 ELISA. Other than providing the IL‐6 data, Pathogenes did not have access to the data until it was presented in the manuscript.
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This article includes 18 references
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Citations
This article has been cited 1 times.- Jaworska J, Ropka-Molik K, Piórkowska K, Szmatoła T, Kowalczyk-Zięba I, Wocławek-Potocka I, Siemieniuch M. Transcriptome Profiling of the Retained Fetal Membranes-An Insight in the Possible Pathogenesis of the Disease.. Animals (Basel) 2021 Mar 3;11(3).
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