FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
BMC veterinary research2019; 15(1); 397; doi: 10.1186/s12917-019-2144-x

Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma.

Abstract: Mild equine asthma is a common inflammatory airway disease of the horse. The primary treatment of mild equine asthma is corticosteroids. The purpose of this study was to investigate the effects of injected dexamethasone on relative IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-17, IL-23, IFN-γ, Eotaxin-2 and TNF-α mRNA expression in bronchoalveolar lavage (BAL) fluid in healthy Thoroughbred horses (n = 6), and those with mild equine asthma (n = 7). Results: Horses with mild equine asthma had a significantly greater bronchoalveolar lavage mast cell percentage than healthy horses both before and after treatment. Mild equine asthma was associated with a 4.95-fold up-regulation of IL-17 (p = 0.026) and a 2.54-fold down-regulation of IL-10 (p = 0.049) compared to healthy horses. TNF-α was down-regulated in response to dexamethasone treatment in both healthy horses (3.03-fold, p = 0.023) and those with mild equine asthma (1.75-fold, p = 0.023). IL-5 was also down-regulated in horses with mild asthma (2.17-fold, p = 0.048). Conclusions: Horses with mild equine asthma have a lower concentration of IL-10 in BAL fluid than healthy controls which concurs with human asthmatics. The marked up-regulation of IL-17 in horses with mild asthma suggests these horses had a true tendency of "allergic" airway inflammation in response to environmental allergens. Dexamethasone administration exerted anti-inflammatory effects associated with down-regulation of TNF-α in all horses, and decreased levels of IL-5 mRNA expression in horses with mild equine asthma. The inhibition of the Th-2 response, without any alterations to the airway cytology, indicates that maintained exposure to environmental allergens perpetuates airway inflammation.
Get Full Text
Publication Date: 2019-11-06 PubMed ID: 31694631PubMed Central: PMC6833259DOI: 10.1186/s12917-019-2144-xGoogle 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.
LinkedInCopy
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

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 study evaluates how injected dexamethasone alters the expression of various cytokine mRNAs within bronchial fluids in horses with mild asthma, compared to its effects in healthy horses. The results suggest that horses with mild asthma had distinct differences in cytokine levels and that dexamethasone helped lower the inflammatory responses in these horses.

Research Design and Methodology

  • The research involved studying the effects of dexamethasone, a corticosteroid, on Thoroughbred horses, both healthy ones and those suffering from mild equine asthma.
  • The researchers focused on the expression of a series of cytokines, immune system signalling proteins, within the bronchoalveolar lavage (BAL) fluid of these horses. Cytokines studied included IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-17, IL-23, IFN-γ, Eotaxin-2, and TNF-α.
  • By comparing the expressions of these cytokines before and after dexamethasone treatment, the research aimed to elucidate the biological response to the drug in healthy and asthmatic horses.

Key Findings

  • Horses with mild equine asthma showed a greater percentage of mast cells in BAL fluid both before and after treatment compared to healthy horses.
  • A 4.95-fold up-regulation of IL-17 and 2.54-fold down-regulation of IL-10 was observed in asthmatic horses as compared to healthy ones, indicating distinct differences in cytokine levels.
  • Dexamethasone treatment caused a down-regulation of TNF-α in both categories of horses, indicating its anti-inflammatory properties.
  • Additionally, the treatment down-regulated IL-5 in horses suffering from mild asthma.

Conclusions

  • The results suggest that the lower concentration of IL-10 in BAL fluid of horses with mild asthma is consistent with patterns observed in human asthmatics.
  • The up-regulation of IL-17 points to a true tendency of “allergic” airway inflammation in response to environmental allergens in horses with mild asthma.
  • The research highlighted the anti-inflammatory effects of dexamethasone, as evidenced by the down-regulation of TNF-α in all horses and a decrease in IL-5 mRNA expression in asthmatic horses.
  • Based on the lack of alterations to airway cytology even after dexamethasone treatment, it can be inferred that continued exposure to environmental allergens may perpetuate airway inflammation in asthmatic horses.

Cite This Article

APA
Bond SL, Hundt J, Léguillette R. (2019). Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma. BMC Vet Res, 15(1), 397. https://doi.org/10.1186/s12917-019-2144-x

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 397
PII: 397

Researcher Affiliations

Bond, Stephanie L
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
Hundt, Jana
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
Léguillette, Renaud
  • Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada. rleguill@ucalgary.ca.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Asthma / drug therapy
  • Asthma / veterinary
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dexamethasone / pharmacology
  • Horse Diseases / drug therapy
  • Horses
  • Male
  • Mast Cells / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Conflict of Interest Statement

The authors declare that they have no competing interests.

References

This article includes 40 references
  1. Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
    doi: 10.1111/jvim.13824pmc: PMC4913592pubmed: 26806374google scholar: lookup
  2. Wasko AJ, Barkema HW, Nicol J, Fernandez N, Logie N, Léguillette R. Evaluation of a risk-screening questionnaire to detect equine lung inflammation: results of a large field study.. Equine Vet J 2011 Mar;43(2):145-52.
    doi: 10.1111/j.2042-3306.2010.00150.xpubmed: 21592207google scholar: lookup
  3. Hughes KJ, Nicolson L, Da Costa N, Franklin SH, Allen KJ, Dunham SP. Evaluation of cytokine mRNA expression in bronchoalveolar lavage cells from horses with inflammatory airway disease.. Vet Immunol Immunopathol 2011 Mar 15;140(1-2):82-9.
    doi: 10.1016/j.vetimm.2010.11.018pubmed: 21194756google scholar: lookup
  4. Lavoie JP, Cesarini C, Lavoie-Lamoureux A, Moran K, Lutz S, Picandet V, Jean D, Marcoux M. Bronchoalveolar lavage fluid cytology and cytokine messenger ribonucleic Acid expression of racehorses with exercise intolerance and lower airway inflammation.. J Vet Intern Med 2011 Mar-Apr;25(2):322-9.
    doi: 10.1111/j.1939-1676.2010.0664.xpubmed: 21281348google scholar: lookup
  5. Richard EA, Depecker M, Defontis M, Leleu C, Fortier G, Pitel PH, Couroucé-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.12464pmc: PMC4895612pubmed: 25269933google scholar: lookup
  6. Beekman L, Tohver T, Léguillette R. Comparison of cytokine mRNA expression in the bronchoalveolar lavage fluid of horses with inflammatory airway disease and bronchoalveolar lavage mastocytosis or neutrophilia using REST software analysis.. J Vet Intern Med 2012 Jan-Feb;26(1):153-61.
    doi: 10.1111/j.1939-1676.2011.00847.xpubmed: 22168153google scholar: lookup
  7. Bond S, Léguillette 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.15302pmc: PMC6271326pubmed: 30294851google scholar: lookup
  8. Giguère S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.. Vet Immunol Immunopathol 2002 Mar;85(3-4):147-58.
    doi: 10.1016/S0165-2427(01)00420-2pubmed: 11943316google scholar: lookup
  9. DeLuca L, Erb HN, Young JC, Perkins GA, Ainsworth DM. The effect of adding oral dexamethasone to feed alterations on the airway cell inflammatory gene expression in stabled horses affected with recurrent airway obstruction.. J Vet Intern Med 2008 Mar-Apr;22(2):427-35.
    doi: 10.1111/j.1939-1676.2008.0055.xpubmed: 18346142google scholar: lookup
  10. Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP. Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma.. Sci Rep 2017 Aug 18;7(1):8843.
    doi: 10.1038/s41598-017-09414-8pmc: PMC5562887pubmed: 28821845google scholar: lookup
  11. Léguillette 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.
    doi: 10.1111/jvim.14740pmc: PMC5508307pubmed: 28568169google scholar: lookup
  12. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR.. Nucleic Acids Res 2002 May 1;30(9):e36.
    doi: 10.1093/nar/30.9.e36pmc: PMC113859pubmed: 11972351google scholar: lookup
  13. Chini V, Foka A, Dimitracopoulos G, Spiliopoulou I. Absolute and relative real-time PCR in the quantification of tst gene expression among methicillin-resistant Staphylococcus aureus: evaluation by two mathematical models.. Lett Appl Microbiol 2007 Nov;45(5):479-84.
    doi: 10.1111/j.1472-765X.2007.02208.xpubmed: 17958553google scholar: lookup
  14. Beekman L, Tohver T, Dardari R, Léguillette 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.
    doi: 10.1186/1471-2199-12-5pmc: PMC3039571pubmed: 21272375google scholar: lookup
  15. Lavoie JP, Léguillette R, Pasloske K, Charette L, Sawyer N, Guay D, Murphy T, Hickey GJ. Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction.. Am J Vet Res 2002 Apr;63(4):579-85.
    doi: 10.2460/ajvr.2002.63.579pubmed: 11939323google scholar: lookup
  16. Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G, Couture C, Martin JG, Lavoie JP. Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model.. Am J Respir Cell Mol Biol 2012 Nov;47(5):589-96.
    doi: 10.1165/rcmb.2011-0363OCpubmed: 22721832google scholar: lookup
  17. Lavoie JP, Pasloske K, Joubert P, Cordeau ME, Mancini J, Girard Y, Friesen RW, Frenette R, Blouin M, Young RN, Hickey G. Lack of clinical efficacy of a phosphodiesterase-4 inhibitor for treatment of heaves in horses.. J Vet Intern Med 2006 Jan-Feb;20(1):175-81.
    doi: 10.1111/j.1939-1676.2006.tb02838.xpubmed: 16496938google scholar: lookup
  18. Picandet V, Léguillette R, Lavoie JP. Comparison of efficacy and tolerability of isoflupredone and dexamethasone in the treatment of horses affected with recurrent airway obstruction ('heaves').. Equine Vet J 2003 Jun;35(4):419-24.
    doi: 10.2746/042516403776014208pubmed: 12880012google scholar: lookup
  19. Duz M, Whittaker AG, Love S, Parkin TD, Hughes KJ. Validation of a digital audio recording method for the objective assessment of cough in the horse.. Res Vet Sci 2010 Oct;89(2):266-71.
    doi: 10.1016/j.rvsc.2010.03.005pubmed: 20363008google scholar: lookup
  20. Holcombe SJ, Jackson C, Gerber V, Jefcoat A, Berney C, Eberhardt S, Robinson NE. Stabling is associated with airway inflammation in young Arabian horses.. Equine Vet J 2001 May;33(3):244-9.
    doi: 10.2746/042516401776249606pubmed: 11352345google scholar: lookup
  21. Gerber V, Robinson NE, Luethi S, Marti E, Wampfler B, Straub R. Airway inflammation and mucus in two age groups of asymptomatic well-performing sport horses.. Equine Vet J 2003 Jul;35(5):491-5.
    doi: 10.2746/042516403775600424pubmed: 12875328google scholar: lookup
  22. Millerick-May ML, Karmaus W, Derksen FJ, Berthold B, Holcombe SJ, Robinson NE. Local airborne particulate concentration is associated with visible tracheal mucus in Thoroughbred racehorses.. Equine Vet J 2013 Jan;45(1):85-90.
    doi: 10.1111/j.2042-3306.2012.00568.xpubmed: 22494157google scholar: lookup
  23. Ivester KM, Couëtil 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.
    doi: 10.1111/jvim.12458pmc: PMC4895611pubmed: 25273818google scholar: lookup
  24. Robinson NE, Karmaus W, Holcombe SJ, Carr EA, Derksen FJ. Airway inflammation in Michigan pleasure horses: prevalence and risk factors.. Equine Vet J 2006 Jul;38(4):293-9.
    doi: 10.2746/042516406777749281pubmed: 16866194google scholar: lookup
  25. Gerber V, Schott Ii HC, Robinson NE. Owner assessment in judging the efficacy of airway disease treatment.. Equine Vet J 2011 Mar;43(2):153-8.
    doi: 10.1111/j.2042-3306.2010.00156.xpubmed: 21592208google scholar: lookup
  26. McFarlane D, Holbrook TC. Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction.. J Vet Intern Med 2008 Mar-Apr;22(2):436-42.
    doi: 10.1111/j.1939-1676.2008.0076.xpubmed: 18371032google scholar: lookup
  27. Hansen S, Sun L, Baptiste KE, Fjeldborg J, Horohov DW. Age-related changes in intracellular expression of IFN-γ and TNF-α in equine lymphocytes measured in bronchoalveolar lavage and peripheral blood.. Dev Comp Immunol 2013 Mar;39(3):228-33.
    doi: 10.1016/j.dci.2012.11.007pubmed: 23219905google scholar: lookup
  28. Wang YH, Wills-Karp M. The potential role of interleukin-17 in severe asthma.. Curr Allergy Asthma Rep 2011 Oct;11(5):388-94.
    doi: 10.1007/s11882-011-0210-ypmc: PMC4115366pubmed: 21773747google scholar: lookup
  29. Borish L, Aarons A, Rumbyrt J, Cvietusa P, Negri J, Wenzel S. Interleukin-10 regulation in normal subjects and patients with asthma.. J Allergy Clin Immunol 1996 Jun;97(6):1288-96.
    doi: 10.1016/S0091-6749(96)70197-5pubmed: 8648025google scholar: lookup
  30. Rosenwasser LJ, Borish L. Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies (IL-4 and IL-10).. Am J Respir Crit Care Med 1997 Oct;156(4 Pt 2):S152-5.
    doi: 10.1164/ajrccm.156.4.12tac-14pubmed: 9351597google scholar: lookup
  31. Barnes PJ. Th2 cytokines and asthma: an introduction.. Respir Res 2001;2(2):64-5.
    doi: 10.1186/rr39pmc: PMC59569pubmed: 11686866google scholar: lookup
  32. Riihimäki 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.
    pmc: PMC2568048pubmed: 19086376
  33. Ivester KM, Couëtil LL, Moore GE, Zimmerman NJ, Raskin RE. Environmental exposures and airway inflammation in young thoroughbred horses.. J Vet Intern Med 2014 May-Jun;28(3):918-24.
    doi: 10.1111/jvim.12333pmc: PMC4895475pubmed: 24773603google scholar: lookup
  34. Eum SY, Maghni K, Hamid Q, Eidelman DH, Campbell H, Isogai S, Martin JG. Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: role of eosinophils, IL-5, eotaxin, and IL-13.. J Allergy Clin Immunol 2003 May;111(5):1049-61.
    doi: 10.1067/mai.2003.1416pubmed: 12743570google scholar: lookup
  35. Jiang XG, Yang XD, Lv Z, Zhuang PH. Elevated serum levels of TNF-α, IL-8, and ECP can be involved in the development and progression of bronchial asthma.. J Asthma 2018 Feb;55(2):111-118.
    doi: 10.1080/02770903.2017.1318141pubmed: 28399677google scholar: lookup
  36. Liu G, Zhu R, Li B. TNF-alpha and IL-8 of the patients with allergic asthma.. J Huazhong Univ Sci Technolog Med Sci 2005;25(3):274-5, 309.
    doi: 10.1007/BF02828140pubmed: 16201269google scholar: lookup
  37. Bond SL, Timsit E, Workentine M, Alexander T, Léguillette R. Upper and lower respiratory tract microbiota in horses: bacterial communities associated with health and mild asthma (inflammatory airway disease) and effects of dexamethasone.. BMC Microbiol 2017 Aug 23;17(1):184.
    doi: 10.1186/s12866-017-1092-5pmc: PMC5569571pubmed: 28835202google scholar: lookup
  38. Fernandez NJ, Hecker KG, Gilroy CV, Warren AL, Léguillette R. Reliability of 400-cell and 5-field leukocyte differential counts for equine bronchoalveolar lavage fluid.. Vet Clin Pathol 2013 Mar;42(1):92-8.
    doi: 10.1111/vcp.12013pubmed: 23289790google scholar: lookup
  39. Giguère S, Prescott JF. Quantitation of equine cytokine mRNA expression by reverse transcription-competitive polymerase chain reaction.. Vet Immunol Immunopathol 1999 Jan 4;67(1):1-15.
    doi: 10.1016/S0165-2427(98)00212-8pubmed: 9950350google scholar: lookup
  40. Léguillette R, Laviolette M, Bergeron C, Zitouni N, Kogut P, Solway J, Kachmar L, Hamid Q, Lauzon AM. Myosin, transgelin, and myosin light chain kinase: expression and function in asthma.. Am J Respir Crit Care Med 2009 Feb 1;179(3):194-204.
    doi: 10.1164/rccm.200609-1367OCpmc: PMC2633053pubmed: 19011151google scholar: lookup

Citations

This article has been cited 9 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. Adamič N, Prpar Mihevc S, Blagus R, Kramarič P, Krapež U, Majdič 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.
    doi: 10.1186/s13287-022-02704-7pubmed: 35063028google scholar: lookup
  4. Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review. J Vet Intern Med 2021 Jul;35(4):2045-2057.
    doi: 10.1111/jvim.16189pubmed: 34085342google scholar: lookup
  5. Zajkowska M, Mroczko B. From Allergy to Cancer-Clinical Usefulness of Eotaxins. Cancers (Basel) 2021 Jan 3;13(1).
    doi: 10.3390/cancers13010128pubmed: 33401527google scholar: lookup
  6. Sanz MG, Jellen G, Cody L, Bergsma J, Cha M, Kogan C, Kordas G, Bayly WM, Leguillette R. Use of inhaled ciclesonide for treatment of moderate asthma in Thoroughbred racehorses. J Vet Intern Med 2025 Mar-Apr;39(2):e17267.
    doi: 10.1111/jvim.17267pubmed: 39945569google scholar: lookup
  7. Woodrow JS, Hopster K, Palmisano M, Payette F, Kulp J, Stefanovski D, Nolen-Walston R. Time to resolution of airway inflammation caused by bronchoalveolar lavage in healthy horses. J Vet Intern Med 2024 Sep-Oct;38(5):2776-2782.
    doi: 10.1111/jvim.17169pubmed: 39198933google scholar: lookup
  8. Bell T, Kyriazopoulou P, Mowbray C, Murphy BA. Equine Headshaking Syndrome: Triggers, Seasonality, and Treatment Efficacy in Australia. Animals (Basel) 2024 Mar 13;14(6).
    doi: 10.3390/ani14060875pubmed: 38539973google scholar: lookup
  9. Bond S, Léguillette R. A CONSORT-guided, randomized controlled clinical trial of nebulized administration of dexamethasone and saline on lower airway cytokine mRNA expression in horses with moderate asthma. J Vet Intern Med 2024 Mar-Apr;38(2):1214-1223.
    doi: 10.1111/jvim.16983pubmed: 38205666google scholar: lookup
Subscribe to our newsletter
Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.