Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.
Abstract: Work in humans and laboratory animals has identified a central role for cytokines and chemokines in development and persistence of lower airway inflammation. The objectives of this study were to determine interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha induction in bronchoalveolar lavage (BAL) of control horses and horses with heaves both during remission and exacerbation of the disease, and to determine the effect of therapy with inhaled fluticasone propionate on the cytokine profile of horses with heaves. IL-1 beta and TNF-alpha mRNA expression was significantly higher in horses with heaves after exposure to moldy hay compared to either values obtained during clinical remission or to healthy controls. IL-8 mRNA expression and protein concentrations were significantly higher in horses with heaves than in controls. Both IL-4 and IFN-gamma mRNA expression was increased at various times in heaves-susceptible horses compared to controls. IL-2, IL-5 and IL-10 mRNA expression was not detected in BAL cells of either group. Therapy with inhaled fluticasone propionate after induction of a severe heaves exacerbation resulted in complete resolution of clinical signs, normalization of pulmonary function tests, and significant decrease in BAL neutrophilia. This was associated with a significant decrease in IL-4 mRNA expression and increase in IFN-gamma/IL-4 ratio in horses with heaves. These results demonstrate the clinical efficacy of inhaled fluticasone propionate for the treatment of heaves and suggest a role for cytokines in the development of lower airway inflammation in heaves-susceptible horses.
Publication Date: 2002-04-12 PubMed ID: 11943316DOI: 10.1016/s0165-2427(01)00420-2Google 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
- Bronchoalveolar Lavage
- Clinical Study
- Clinical Symptoms
- Cytokines
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Disease Treatment
- Equine Health
- Horses
- Immune Response
- In Vivo
- Inflammation
- Inflammatory Response
- Interleukins
- Lung Health
- Pharmacology
- Recurrent Airway Obstruction
- Respiratory Health
- Veterinary Medicine
- Veterinary Research
Summary
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The research shows that cytokines, substances secreted by specific cells of the immune system, are involved in the onset and progression of lower airway inflammation in horses with a respiratory condition called heaves. Moreover, the study finds that treatment with an inhaled medication called fluticasone propionate can effectively alleviate the symptoms of heaves.
Objectives and Methods of the Study
- The objectives of this research were to study the induction of various interleukins (IL) and other cytokines in horses with heaves during the different stages of the disease, and to investigate the effects of therapy with inhaled fluticasone propionate on the cytokine profile of these horses.
- The research carried out Bronchoalveolar lavage (BAL), a medical procedure in which a bronchoscope is passed through the mouth or nose into the lungs and fluid is squirted into a small part of the lung and then collected for examination.
- In BAL fluids, the study tested for the presence of several cytokines such as IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, and TNF-alpha.
Findings
- Increased IL-1 beta and TNF-alpha mRNA expression was found in horses with heaves after exposure to moldy hay compared to when the disease was in remission or in healthy horses. mRNA expression is the process that converts the information coded in a gene to a final gene product.
- Both IL-4 and IFN-gamma mRNA expressions were found to be higher in affected horses at various times compared to healthy horses.
- Interestingly, expression of IL-2, IL-5, and IL-10 mRNA was not detected in BAL cells of either the controls or horses with heaves.
Therapy Outcomes
- Administration of inhaled fluticasone propionate after an intense flare-up of heaves led to complete resolution of clinical signs, normalization of lung function tests, and a significant reduction in BAL neutrophilia (an increased level of immune cells called neutrophils which is often a sign of inflammation).
- Therapy was associated with a decrease in IL-4 mRNA expression and an increase in the ratio of IFN-gamma to IL-4, potentially indicative of a favorable immune response.
Conclusion
- The study demonstrates the clinical efficacy of inhaled fluticasone propionate for treatment of heaves in horses. It confirms previous observations in humans and lab animals that cytokines play a crucial role in lower airway inflammation.
Cite This Article
APA
Giguu00e8re S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M.
(2002).
Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.
Vet Immunol Immunopathol, 85(3-4), 147-158.
https://doi.org/10.1016/s0165-2427(01)00420-2 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, P.O. Box 100136, Gainesville, FL 32610, USA. gigueres@mail.vetmed.ufl.edu
MeSH Terms
- Androstadienes / immunology
- Androstadienes / therapeutic use
- Animals
- Anti-Inflammatory Agents / immunology
- Anti-Inflammatory Agents / therapeutic use
- Bronchoalveolar Lavage Fluid / chemistry
- Bronchoalveolar Lavage Fluid / cytology
- Bronchoalveolar Lavage Fluid / immunology
- Cell Count / veterinary
- Cytokines / analysis
- Cytokines / biosynthesis
- Cytokines / genetics
- Fluticasone
- Horse Diseases / drug therapy
- Horse Diseases / immunology
- Horse Diseases / metabolism
- Horses
- Lung Diseases / drug therapy
- Lung Diseases / immunology
- Lung Diseases / metabolism
- Lung Diseases / veterinary
- RNA, Messenger / biosynthesis
- RNA, Messenger / genetics
- Respiratory Function Tests / veterinary
- Reverse Transcriptase Polymerase Chain Reaction / veterinary
- Statistics, Nonparametric
Citations
This article has been cited 44 times.- Frippiat T, Art T, Tosi I. Airway Hyperresponsiveness, but Not Bronchoalveolar Inflammatory Cytokines Profiles, Is Modified at the Subclinical Onset of Severe Equine Asthma.. Animals (Basel) 2023 Aug 1;13(15).
- Woodrow JS, Sheats MK, Cooper B, Bayless R. Asthma: The Use of Animal Models and Their Translational Utility.. Cells 2023 Apr 5;12(7).
- 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.
- Rutledge JJ, Paegelow J, Ritchey J, Singh A, Rizzi T, Murray C, Gilliam L, Crisman E, Williams NJ, Holbrook TC. Nebulized glycosylated caffeic acid phenylether ester attenuation of environmental particulate-induced airway inflammation in horses.. Front Vet Sci 2022;9:958567.
- 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).
- 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).
- Adamiu010d N, Prpar Mihevc S, Blagus R, Kramariu010d P, Krapeu017e U, Majdiu010d G, Viel L, Hoffman AM, Bienzle D, Vengust M. Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma.. Stem Cell Res Ther 2022 Jan 21;13(1):23.
- Mainguy-Seers S, Boivin R, Pourali Dogaheh S, Beaudry F, Hu00e9lie P, Bonilla AG, Martin JG, Lavoie JP. Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses.. Sci Rep 2022 Jan 10;12(1):446.
- 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).
- Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review.. J Vet Intern Med 2021 Jul;35(4):2045-2057.
- 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).
- Larson EM, Babasyan S, Wagner B. IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy.. J Immunol 2021 May 15;206(10):2312-2321.
- 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).
- Hue E, Orard M, Toquet MP, Depecker M, Couroucu00e9 A, Pronost S, Paillot R, Richard EA. Asymmetrical Pulmonary Cytokine Profiles Are Linked to Bronchoalveolar Lavage Fluid Cytology of Horses With Mild Airway Neutrophilia.. Front Vet Sci 2020;7:226.
- Bond SL, Hundt J, Lu00e9guillette R. Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma.. BMC Vet Res 2019 Nov 6;15(1):397.
- Klier J, Bartl C, Geuder S, Geh KJ, Reese S, Goehring LS, Winter G, Gehlen H. Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect.. Immun Inflamm Dis 2019 Sep;7(3):130-149.
- Morales N, Henriquez C, Sarmiento J, Uberti B, Moran G. Tamoxifen inhibits chemokinesis in equine neutrophils.. Ir Vet J 2018;71:22.
- 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.
- Lavoie JP, Leclere M, Rodrigues N, Lemos KR, Bourzac C, Lefebvre-Lavoie J, Beauchamp G, Albrecht B. Efficacy of inhaled budesonide for the treatment of severe equine asthma.. Equine Vet J 2019 May;51(3):401-407.
- Husulak ML, Manning ST, Meachem MD, Burgess HJ, Epp TY, Montgomery JB. Does antimicrobial therapy improve outcomes in horses with severe equine asthma and a positive tracheal wash bacterial culture?. Can J Vet Res 2018 Jul;82(3):184-191.
- Rosenberg HF, Druey KM. Modeling asthma: Pitfalls, promises, and the road ahead.. J Leukoc Biol 2018 Jul;104(1):41-48.
- 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.
- Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes.. Front Vet Sci 2017;4:160.
- Lu00e9guillette R, Tohver T, Bond SL, Nicol JA, McDonald KJ. Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease.. J Vet Intern Med 2017 Jul;31(4):1193-1201.
- Barton AK, Pelli A, Rieger M, Gehlen H. Procalcitonin as a biomarker in equine chronic pneumopathies.. BMC Vet Res 2016 Dec 9;12(1):281.
- Ru00fctten S, Schusser GF, Abraham G, Schru00f6dl W. Release kinetics of tumor necrosis factor-u03b1 and interleukin-1 receptor antagonist in the equine whole blood.. BMC Vet Res 2016 Jun 17;12(1):117.
- Couu00ebtil LL, Cardwell JM, Gerber V, Lavoie JP, Lu00e9guillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
- Korn A, Miller D, Dong L, Buckles EL, Wagner B, Ainsworth DM. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response.. PLoS One 2015;10(11):e0142622.
- Sandersen C, Bienzle D, Cerri S, Franck T, Derochette S, Neven P, Mouytis-Mickalad A, Serteyn D. Effect of inhaled hydrosoluble curcumin on inflammatory markers in broncho-alveolar lavage fluid of horses with LPS-induced lung neutrophilia.. Multidiscip Respir Med 2015;10(1):16.
- Ivester KM, Couu00ebtil LL, Zimmerman NJ. Investigating the link between particulate exposure and airway inflammation in the horse.. J Vet Intern Med 2014 Nov-Dec;28(6):1653-65.
- 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.
- 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.
- 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.
- 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.
- Beekman L, Tohver T, Dardari R, Lu00e9guillette R. Evaluation of suitable reference genes for gene expression studies in bronchoalveolar lavage cells from horses with inflammatory airway disease.. BMC Mol Biol 2011 Jan 28;12:5.
- Ramery E, Fievez L, Fraipont A, Bureau F, Lekeux P. Characterization of pentraxin 3 in the horse and its expression in airways.. Vet Res 2010 Mar-Apr;41(2):18.
- 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.
- Riihimu00e4ki M, Raine A, Elfman L, Pringle J. Markers of respiratory inflammation in horses in relation to seasonal changes in air quality in a conventional racing stable.. Can J Vet Res 2008 Oct;72(5):432-9.
- Riihimu00e4ki M, Raine A, Pourazar J, Sandstru00f6m T, Art T, Lekeux P, Couu00ebtil L, Pringle J. Epithelial expression of mRNA and protein for IL-6, IL-10 and TNF-alpha in endobronchial biopsies in horses with recurrent airway obstruction.. BMC Vet Res 2008 Feb 23;4:8.
- Theegarten D, Sachse K, Mentrup B, Fey K, Hotzel H, Anhenn O. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease.. Respir Res 2008 Jan 29;9(1):14.
- 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.
- 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.
- 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.
- 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.