American journal of respiratory and critical care medicine2001; 164(8 Pt 1); 1410-1413; doi: 10.1164/ajrccm.164.8.2012091

Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile.

Abstract: Heaves in horses shares many similarities with human asthma, including lower airway inflammation, reversible airway obstruction, and bronchial hyperresponsiveness. Extrinsic asthma is an allergic response to environmental allergens and a similar immunologic mechanism may be implicated in heaves. It is now recognized that a Th2 subset of CD4+ lymphocytes is associated with allergic diseases such as atopic asthma. The purpose of this study was to determine whether airway inflammation in heaves is associated with a pattern of expression of cytokine suggestive of a Th2 type response. The expression of mRNA, encoding interleukin (IL)-4, IL-5, and interferon gamma (IFN-gamma) was measured in bronchoalveolar cells from seven horses with heaves and five control horses, using in situ hybridization and radiolabeled equine-specific cRNA probes coding for these cytokines. Bronchoalveolar cells of horses with heaves had an increased expression of IL-4 (p = 0.01) and IL-5 (p = 0.02) mRNA and a decreased expression of INF-gamma (p = 0.01) compared with control horses. Here we show that inflammatory cells in lungs from horses with heaves display a Th2-type cytokine profile that is consistent with the hypothesis that heaves is an allergic condition with similarity to human asthma.
Publication Date: 2001-11-13 PubMed ID: 11704587DOI: 10.1164/ajrccm.164.8.2012091Google Scholar: Lookup
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.

The article reviews a study aimed at understanding the type of immune response (Th2-type) associated with a respiratory disease in horses, commonly called ‘heaves’, which holds similarities to human asthma. It focuses on analyzing the expression of specific cytokines in bronchoalveolar cells from both affected and unaffected horses.

Introduction

  • The study explores heaves in horses, which is similar to human asthma including lower airway inflammation, reversible airway obstruction, and bronchial hyperresponsiveness.
  • The disease can be associated with an allergic response to environmental allergens, implying an immunologic mechanism at play.
  • The research aims to establish if inflammation in heaves is linked with a Th2 type response, a subset of CD4+ lymphocytes associated with allergic diseases.

Methods

  • The study measures the expression of mRNA – encoding interleukin (IL)-4, IL-5, and interferon gamma (IFN-gamma) – in bronchoalveolar cells from seven horses with heaves and five control horses.
  • This is done by using in situ hybridization and radiolabeled equine-specific cRNA probes that code for these cytokines.

Findings

  • The bronchoalveolar cells of horses diagnosed with heaves showed increased expression of IL-4 and IL-5 mRNA, with decreased expression of INF-gamma, in comparison to the control horses.
  • This suggests that the immune cells in the lungs of horses with heaves present a Th2 type cytokine profile.

Conclusion

  • The results of the study align with the hypothesis that heaves is an allergic condition exhibiting a Th2-type cytokine profile, akin to human asthma.
  • This understanding can have implications on the management and potential treatment of the disease, contributing to equine health.

Cite This Article

APA
Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA. (2001). Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile. Am J Respir Crit Care Med, 164(8 Pt 1), 1410-1413. https://doi.org/10.1164/ajrccm.164.8.2012091

Publication

ISSN: 1073-449X
NlmUniqueID: 9421642
Country: United States
Language: English
Volume: 164
Issue: 8 Pt 1
Pages: 1410-1413

Researcher Affiliations

Lavoie, J P
  • Facultu00e9 de Mu00e9decine Vu00e9tu00e9rinaire, Universitu00e9 de Montru00e9al, St-Hyacinthe, Quu00e9bec, Canada. Jean-Pierre.Lavoie@umontreal.ca
Maghni, K
    Desnoyers, M
      Taha, R
        Martin, J G
          Hamid, Q A

            MeSH Terms

            • Animals
            • Asthma / immunology
            • Asthma / veterinary
            • Bronchoalveolar Lavage Fluid / cytology
            • Cytokines / biosynthesis
            • Cytokines / genetics
            • Horse Diseases / immunology
            • Horses
            • Inflammation / immunology
            • Inflammation / veterinary
            • Neutrophils / immunology
            • RNA, Messenger / biosynthesis
            • Th2 Cells / immunology

            Citations

            This article has been cited 40 times.
            1. Woodrow JS, Sheats MK, Cooper B, Bayless R. Asthma: The Use of Animal Models and Their Translational Utility.. Cells 2023 Apr 5;12(7).
              doi: 10.3390/cells12071091pubmed: 37048164google scholar: lookup
            2. Woodrow JS, Hines M, Sommardahl C, Flatland B, Lo Y, Wang Z, Sheats MK, Lennon EM. Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma.. Front Vet Sci 2022;9:997139.
              doi: 10.3389/fvets.2022.997139pubmed: 36713876google scholar: lookup
            3. Klier J, Fuchs S, Winter G, Gehlen H. Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment.. Animals (Basel) 2022 Aug 16;12(16).
              doi: 10.3390/ani12162087pubmed: 36009677google scholar: lookup
            4. Gressler AE, Lu00fcbke S, Wagner B, Arnold C, Lohmann KL, Schnabel CL. Comprehensive Flow Cytometric Characterization of Bronchoalveolar Lavage Cells Indicates Comparable Phenotypes Between Asthmatic and Healthy Horses But Functional Lymphocyte Differences.. Front Immunol 2022;13:896255.
              doi: 10.3389/fimmu.2022.896255pubmed: 35874777google scholar: lookup
            5. Basano I, Romolo A, Iamone G, Memoli G, Riccio B, Lavoie JP, Miniscalco B, Bullone M. Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma.. Animals (Basel) 2022 Apr 20;12(9).
              doi: 10.3390/ani12091070pubmed: 35565497google scholar: lookup
            6. Simu00f5es J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
              doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
            7. Kang H, Bienzle D, Lee GKC, Pichu00e9 u00c9, Viel L, Odemuyiwa SO, Beeler-Marfisi J. Flow cytometric analysis of equine bronchoalveolar lavage fluid cells in horses with and without severe equine asthma.. Vet Pathol 2022 Jan;59(1):91-99.
              doi: 10.1177/03009858211042588pubmed: 34521286google scholar: lookup
            8. Lo Feudo CM, Stucchi L, Alberti E, Conturba B, Zucca E, Ferrucci F. Intradermal Testing Results in Horses Affected by Mild-Moderate and Severe Equine Asthma.. Animals (Basel) 2021 Jul 13;11(7).
              doi: 10.3390/ani11072086pubmed: 34359214google scholar: lookup
            9. Morini M, Peli A, Rinnovati R, Magazzu00f9 G, Romagnoli N, Spadari A, Pietra M. Immunohistochemical Expression of Neurokinin-A and Interleukin-8 in the Bronchial Epithelium of Horses with Severe Equine Asthma Syndrome during Asymptomatic, Exacerbation, and Remission Phase.. Animals (Basel) 2021 May 12;11(5).
              doi: 10.3390/ani11051376pubmed: 34066204google scholar: lookup
            10. Millares-Ramirez EM, Lavoie JP. Bronchial angiogenesis in horses with severe asthma and its response to corticosteroids.. J Vet Intern Med 2021 Jul;35(4):2026-2034.
              doi: 10.1111/jvim.16159pubmed: 34048095google scholar: lookup
            11. Davis KU, Sheats MK. Differential gene expression and Ingenuity Pathway Analysis of bronchoalveolar lavage cells from horses with mild/moderate neutrophilic or mastocytic inflammation on BAL cytology.. Vet Immunol Immunopathol 2021 Apr;234:110195.
              doi: 10.1016/j.vetimm.2021.110195pubmed: 33588285google scholar: lookup
            12. Davis KU, Sheats MK. The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses.. Inflammation 2021 Apr;44(2):450-465.
              doi: 10.1007/s10753-020-01362-2pubmed: 33150539google scholar: lookup
            13. Ceriotti S, Bullone M, Leclere M, Ferrucci F, Lavoie JP. Severe asthma is associated with a remodeling of the pulmonary arteries in horses.. PLoS One 2020;15(10):e0239561.
              doi: 10.1371/journal.pone.0239561pubmed: 33091038google scholar: lookup
            14. Hulliger MF, Pacholewska A, Vargas A, Lavoie JP, Leeb T, Gerber V, Jagannathan V. An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans.. Genes (Basel) 2020 Sep 28;11(10).
              doi: 10.3390/genes11101143pubmed: 32998415google scholar: lookup
            15. Ribitsch I, Baptista PM, Lange-Consiglio A, Melotti L, Patruno M, Jenner F, Schnabl-Feichter E, Dutton LC, Connolly DJ, van Steenbeek FG, Dudhia J, Penning LC. Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do.. Front Bioeng Biotechnol 2020;8:972.
              doi: 10.3389/fbioe.2020.00972pubmed: 32903631google scholar: lookup
            16. Lavoie JP, Bullone M, Rodrigues N, Germim P, Albrecht B, von Salis-Soglio M. Effect of different doses of inhaled ciclesonide on lung function, clinical signs related to airflow limitation and serum cortisol levels in horses with experimentally induced mild to severe airway obstruction.. Equine Vet J 2019 Nov;51(6):779-786.
              doi: 10.1111/evj.13093pubmed: 30854685google scholar: lookup
            17. Tessier L, Cu00f4tu00e9 O, Clark ME, Viel L, Diaz-Mu00e9ndez A, Anders S, Bienzle D. Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma.. Sci Rep 2018 Nov 6;8(1):16408.
              doi: 10.1038/s41598-018-34636-9pubmed: 30401798google scholar: lookup
            18. Morales N, Henriquez C, Sarmiento J, Uberti B, Moran G. Tamoxifen inhibits chemokinesis in equine neutrophils.. Ir Vet J 2018;71:22.
              doi: 10.1186/s13620-018-0133-1pubmed: 30386589google scholar: lookup
            19. Tessier L, Cu00f4tu00e9 O, Bienzle D. Sequence variant analysis of RNA sequences in severe equine asthma.. PeerJ 2018;6:e5759.
              doi: 10.7717/peerj.5759pubmed: 30324028google scholar: lookup
            20. Bond S, Lu00e9guillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS. Equine asthma: Integrative biologic relevance of a recently proposed nomenclature.. J Vet Intern Med 2018 Nov;32(6):2088-2098.
              doi: 10.1111/jvim.15302pubmed: 30294851google scholar: lookup
            21. Mainguy-Seers S, Picotte K, Lavoie JP. Efficacy of tamoxifen for the treatment of severe equine asthma.. J Vet Intern Med 2018 Sep;32(5):1748-1753.
              doi: 10.1111/jvim.15289pubmed: 30084157google scholar: lookup
            22. Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP. Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma.. Respir Res 2017 Dec 12;18(1):207.
              doi: 10.1186/s12931-017-0689-4pubmed: 29233147google scholar: lookup
            23. Bullone M, Lavoie JP. The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma.. Int J Mol Sci 2017 Dec 5;18(12).
              doi: 10.3390/ijms18122612pubmed: 29206130google scholar: lookup
            24. Klier J, Geis S, Steuer J, Geh K, Reese S, Fuchs S, Mueller RS, Winter G, Gehlen H. A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma-affected horses, an animal model.. Immun Inflamm Dis 2018 Mar;6(1):81-96.
              doi: 10.1002/iid3.198pubmed: 29094511google scholar: lookup
            25. Barton AK, Gehlen H. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?. Mediators Inflamm 2016;2016:5693205.
              doi: 10.1155/2016/5693205pubmed: 28053371google scholar: lookup
            26. Pacholewska A, Jagannathan V, Dru00f6gemu00fcller M, Klukowska-Ru00f6tzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.. PLoS One 2015;10(8):e0136103.
              doi: 10.1371/journal.pone.0136103pubmed: 26292153google scholar: lookup
            27. Richard EA, Depecker M, Defontis M, Leleu C, Fortier G, Pitel PH, Couroucu00e9-Malblanc A. Cytokine concentrations in bronchoalveolar lavage fluid from horses with neutrophilic inflammatory airway disease.. J Vet Intern Med 2014 Nov-Dec;28(6):1838-44.
              doi: 10.1111/jvim.12464pubmed: 25269933google scholar: lookup
            28. Sarmiento J, Perez B, Morales N, Henriquez C, Vidal L, Folch H, Galecio JS, Moru00e1n G. Apoptotic effects of tamoxifen on leukocytes from horse peripheral blood and bronchoalveolar lavage fluid.. Vet Res Commun 2013 Dec;37(4):333-8.
              doi: 10.1007/s11259-013-9571-0pubmed: 23846832google scholar: lookup
            29. Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P. Increased hypoxia-inducible factor 1u03b1 expression in lung cells of horses with recurrent airway obstruction.. BMC Vet Res 2012 May 23;8:64.
              doi: 10.1186/1746-6148-8-64pubmed: 22621400google scholar: lookup
            30. Klier J, Fuchs S, May A, Schillinger U, Plank C, Winter G, Coester C, Gehlen H. A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.. Pharm Res 2012 Jun;29(6):1650-7.
              doi: 10.1007/s11095-012-0686-8pubmed: 22302522google scholar: lookup
            31. Racine J, Gerber V, Feutz MM, Riley CP, Adamec J, Swinburne JE, Couetil LL. Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using Ingenuity Pathway Analysisu00ae.. BMC Vet Res 2011 Aug 15;7:48.
              doi: 10.1186/1746-6148-7-48pubmed: 21843342google scholar: lookup
            32. Moran G, Buechner-Maxwell VA, Folch H, Henriquez C, Galecio JS, Perez B, Carrasco C, Barria M. Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction.. Vet Res Commun 2011 Oct;35(7):447-56.
              doi: 10.1007/s11259-011-9482-xpubmed: 21594641google scholar: lookup
            33. Moru00e1n G, Burgos R, Araya O, Folch H. In vitro bioassay to detect reaginic antibodies from the serum of horses affected with recurrent airway obstruction.. Vet Res Commun 2010 Jan;34(1):91-9.
              doi: 10.1007/s11259-009-9334-0pubmed: 20012188google scholar: lookup
            34. Murdoch JR, Lloyd CM. Chronic inflammation and asthma.. Mutat Res 2010 Aug 7;690(1-2):24-39.
              doi: 10.1016/j.mrfmmm.2009.09.005pubmed: 19769993google scholar: lookup
            35. Swinburne JE, Bogle H, Klukowska-Ru00f6tzler J, Dru00f6gemu00fcller M, Leeb T, Temperton E, Dolf G, Gerber V. A whole-genome scan for recurrent airway obstruction in Warmblood sport horses indicates two positional candidate regions.. Mamm Genome 2009 Aug;20(8):504-15.
              doi: 10.1007/s00335-009-9214-5pubmed: 19760324google scholar: lookup
            36. Pietra M, Peli A, Bonato A, Ducci A, Cinotti S. Equine bronchoalveolar lavage cytokines in the development of recurrent airway obstruction.. Vet Res Commun 2007 Aug;31 Suppl 1:313-6.
              doi: 10.1007/s11259-007-0055-ypubmed: 17682903google scholar: lookup
            37. van den Hoven R, Duvigneau JC, Hartl RT, Gemeiner M. Clenbuterol affects the expression of messenger RNA for interleukin 10 in peripheral leukocytes from horses challenged intrabronchially with lipopolysaccharides.. Vet Res Commun 2006 Nov;30(8):921-8.
              doi: 10.1007/s11259-006-3383-4pubmed: 17139543google scholar: lookup
            38. Laan TT, Bull S, van Nieuwstadt RA, Fink-Gremmels J. The effect of aerosolized and intravenously administered clenbuterol and aerosolized fluticasone propionate on horses challenged with Aspergillus fumigatus antigen.. Vet Res Commun 2006 Aug;30(6):623-35.
              doi: 10.1007/s11259-006-3346-9pubmed: 16838204google scholar: lookup
            39. Matera MG, Calzetta L, Peli A, Scagliarini A, Matera C, Cazzola M. Immune sensitization of equine bronchus: glutathione, IL-1beta expression and tissue responsiveness.. Respir Res 2005 Sep 15;6(1):104.
              doi: 10.1186/1465-9921-6-104pubmed: 16164745google scholar: lookup
            40. Szabu00f3 MP, Castagnolli KC, Santana DA, de Castro MB, Romano MA. Amblyomma cajennense ticks induce immediate hypersensitivity in horses and donkeys.. Exp Appl Acarol 2004;33(1-2):109-17.