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Journal of veterinary internal medicine2019; 33(2); 889-896; doi: 10.1111/jvim.15404

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.
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Publication Date: 2019-01-29 PubMed ID: 30693587PubMed Central: PMC6430894DOI: 10.1111/jvim.15404Google Scholar: Lookup
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  • Journal Article

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.

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

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 33
Issue: 2
Pages: 889-896

Researcher Affiliations

Witonsky, Sharon
  • Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
Buechner-Maxwell, Virginia
  • Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
Santonastasto, Amy
  • Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
Pleasant, Robert
  • Large Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
Werre, Stephen
  • Study Design and Statistical Analysis Lab, Virginia Maryland College of Veterinary Medicine, Blacksburg, Virginia.
Wagner, Bettina
  • Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY.
Ellison, Siobhan
  • Pathogenes, Inc, Fairfield, FL.
Lindsay, David
  • 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.

References

This article includes 18 references
  1. Saville WJ, Reed SM, Morley PS, Granstrom DE, Kohn CW, Hinchcliff KW, Wittum TE. Analysis of risk factors for the development of equine protozoal myeloencephalitis in horses.. J Am Vet Med Assoc 2000 Oct 15;217(8):1174-80.
    pubmed: 11043688doi: 10.2460/javma.2000.217.1174google scholar: lookup
  2. Tornquist SJ, Boeder LJ, Mattson DE, Cebra CK, Bildfell RJ, Hamir AN. Lymphocyte responses and immunophenotypes in horses with Sarcocystis neurona infection.. Equine Vet J 2001 Nov;33(7):726-9.
    pubmed: 11770997doi: 10.2746/042516401776249255google scholar: lookup
  3. Spencer JA, Ellison SE, Guarino AJ, Blagburn BL. Cell-mediated immune responses in horses with equine protozoal myeloencephalitis.. J Parasitol 2004 Apr;90(2):428-30.
    pubmed: 15165077doi: 10.1645/ge-3289rngoogle scholar: lookup
  4. Spencer JA, Deinnocentes P, Moyana EM, Guarino AJ, Ellison SE, Bird RC, Blagburn BL. Cytokine gene expression in response to SnSAG1 in horses with equine protozoal myeloencephalitis.. Clin Diagn Lab Immunol 2005 May;12(5):644-6.
    pmc: PMC1112083pubmed: 15879026doi: 10.1128/cdli.12.5.644-646.2005google scholar: lookup
  5. Yang J, Ellison S, Gogal R, Norton H, Lindsay DS, Andrews F, Ward D, Witonsky S. Immune response to Sarcocystis neurona infection in naturally infected horses with equine protozoal myeloencephalitis.. Vet Parasitol 2006 Jun 15;138(3-4):200-10.
    pubmed: 16563631doi: 10.1016/j.vetpar.2006.02.007google scholar: lookup
  6. Witonsky SG, Ellison S, Yang J, Gogal RM, Lawler H, Suzuki Y, Sriranganathan N, Andrews F, Ward D, Lindsay DS. Horses experimentally infected with Sarcocystis neurona develop altered immune responses in vitro.. J Parasitol 2008 Oct;94(5):1047-54.
    pubmed: 18973416doi: 10.1645/ge-1441.1google scholar: lookup
  7. Lewis SR, Ellison SP, Dascanio JJ, Lindsay DS, Gogal RM Jr, Werre SR, Surendran N, Breen ME, Heid BM, Andrews FM, Buechner-Maxwell VA, Witonsky SG. Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model.. J Vet Med 2014;2014:239495.
    pmc: PMC4590861pubmed: 26464923doi: 10.1155/2014/239495google scholar: lookup
  8. Dubey JP, Lindsay DS. Isolation in immunodeficient mice of Sarcocystis neurona from opossum (Didelphis virginiana) faeces, and its differentiation from Sarcocystis falcatula.. Int J Parasitol 1998 Dec;28(12):1823-8.
    pubmed: 9925260doi: 10.1016/s0020-7519(98)00166-0google scholar: lookup
  9. Witonsky SG, Gogal RM Jr, Duncan RB, Lindsay DS. Protective immune response to experimental infection with Sarcocystis neurona in 57BL/6 mice.. J Parasitol 2003 Oct;89(5):924-31.
    pubmed: 14627139doi: 10.1645/ge-67rgoogle scholar: lookup
  10. Witonsky SG, Gogal RM Jr, Duncan RB Jr, Norton H, Ward D, Lindsay DS. Prevention of meningo/encephalomyelitis due to Sarcocystis neurona infection in mice is mediated by CD8 cells.. Int J Parasitol 2005 Jan;35(1):113-23.
    pubmed: 15619522doi: 10.1016/j.ijpara.2004.10.021google scholar: lookup
  11. Mackay R. Equine protozoal myeloencephalitis: treatment, prognosis and prevention.. Clin Tech Equine Pract 2006;5:9‐16.
  12. Chandy ML, Soman C, Kumar SP, Kurup S, Jose R. Understanding molecular mechanisms of levamisole as an anti‐helminthic, anti‐inflammatory, antioxidant, anti‐neoplastic and immunomodulatory drug.. J Oral Maxillofac Surg Med Pathol 2016;28(1):354‐357.
  13. Szeto C, Gillespie KM, Mathieson PW. Levamisole induces interleukin-18 and shifts type 1/type 2 cytokine balance.. Immunology 2000 Jun;100(2):217-24.
    pmc: PMC2327010pubmed: 10886398doi: 10.1046/j.1365-2567.2000.00042.xgoogle scholar: lookup
  14. Chen LY, Lin YL, Chiang BL. Levamisole enhances immune response by affecting the activation and maturation of human monocyte-derived dendritic cells.. Clin Exp Immunol 2008 Jan;151(1):174-81.
    pmc: PMC2276930pubmed: 18005262doi: 10.1111/j.1365-2249.2007.03541.xgoogle scholar: lookup
  15. Hanson KA, Nagel DL, Heidrick ML. Immunomodulatory action of levamisole--I. Structural analysis and immunomodulating activity of levamisole degradation products.. Int J Immunopharmacol 1991;13(6):655-68.
    pubmed: 1752704doi: 10.1016/0192-0561(91)90178-agoogle scholar: lookup
  16. Hanson KA, Heidrick ML. Immunomodulatory action of levamisole--II. Enhancement of concanavalin A response by levamisole is associated with an oxidation degradation product of levamisole formed during lymphocyte culture.. Int J Immunopharmacol 1991;13(6):669-76.
    pubmed: 1752705doi: 10.1016/0192-0561(91)90179-bgoogle scholar: lookup
  17. Krakowski L, Krzyzanowski J, Wrona Z, Siwicki AK. The effect of nonspecific immunostimulation of pregnant mares with 1,3/1,6 glucan and levamisole on the immunoglobulins levels in colostrum, selected indices of nonspecific cellular and humoral immunity in foals in neonatal and postnatal period.. Vet Immunol Immunopathol 1999 Mar 29;68(1):1-11.
    pubmed: 10231947doi: 10.1016/s0165-2427(99)00006-9google scholar: lookup
  18. Witonsky S, Gogal RM Jr, Buechner-Maxwell V, Ahmed SA. Immunologic analysis of blood samples obtained from horses and stored for twenty-four hours.. Am J Vet Res 2003 Aug;64(8):1003-9.
    pubmed: 12926593doi: 10.2460/ajvr.2003.64.1003google scholar: lookup

Citations

This article has been cited 5 times.
  1. 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).
    doi: 10.3390/ani11030675pubmed: 33802481google scholar: lookup
  2. Li K, Yuan L, Zhang J, Li W, Zhao G, Chen Z, Yang Y, He Z, Xiao P. Periplaneta americana extract ameliorates recurrent oral ulcers in rats by enhancing the intestinal epithelial barrier and regulating gut microbiota. PLoS One 2026;21(1):e0340453.
    doi: 10.1371/journal.pone.0340453pubmed: 41575932google scholar: lookup
  3. Zhao M, Huang H, Li B, Pan Y, Wang C, Du W, Wang W, Wang Y, Mao X, Kong X. Preparation of Auricularia auricula-Derived Immune Modulators and Alleviation of Cyclophosphamide-Induced Immune Suppression and Intestinal Microbiota Dysbiosis in Mice. Life (Basel) 2025 Aug 4;15(8).
    doi: 10.3390/life15081236pubmed: 40868884google scholar: lookup
  4. Li Y, Fang Y, Li D, Wu J, Huang Z, Liao X, Liu X, Wei C, Huang Z. Constructing a prognostic model for hepatocellular carcinoma based on bioinformatics analysis of inflammation-related genes. Front Med (Lausanne) 2024;11:1420353.
    doi: 10.3389/fmed.2024.1420353pubmed: 39055701google scholar: lookup
  5. Gholami MH, Rassouli A, Mirzaei S, Hashemi F. The potential immunomodulatory effect of levamisole in humans and farm animals. J Adv Vet Anim Res 2023 Dec;10(4):620-629.
    doi: 10.5455/javar.2023.j717pubmed: 38370882google scholar: lookup
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