Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.
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.
Giguère
Steeve
S
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
Viel
Laurent
L
Lee
Elise
E
MacKay
Robert J
RJ
Hernandez
Jorge
J
Franchini
Marco
M
D000730:Androstadienes / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002452:Cell Count / Q000662:veterinary; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D000068298:Fluticasone; D006734:Horse Diseases / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006736:Horses; D008171:Lung Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012129:Respiratory Function Tests / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D018709:Statistics, Nonparametric
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D012333:RNA, Messenger; D000068298:Fluticasone