A novel model for equine recurrent airway obstruction

Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana, United States
Veterinary Immunology and Immunopathology (Impact Factor: 1.75). 10/2002; 87(3-4):385-9. DOI: 10.1016/S0165-2427(02)00081-8
Source: PubMed

ABSTRACT Equine recurrent airway obstruction (RAO; a term combining both chronic obstructive pulmonary disease (COPD) and summer pasture associated obstructive pulmonary disease (SPAOPD)) is one of the most common equine respiratory diseases with up to 50% of horses affected worldwide. The etiopathogenesis of RAO is unknown although pulmonary hypersensitivity to inhaled mold antigens may be involved. Recent work in our laboratory demonstrating elevated levels of IL-4 and IL-13 mRNA in the airways and peripheral blood of horses with RAO is consistent with an atopic component to RAO. Little is known regarding the earliest phases of RAO in horses. Here we describe the development of a novel airway model for equine RAO that utilizes ovalbumin-coated polystyrene beads for airway sensitization and challenge. Aerosol challenge of sensitized ponies with OVA-coated microbeads resulted in decreased airway compliance, increased percentage of lymphocytes and neutrophils in the bronchoalveolar lavage fluid, and evidence of a Th2 cytokine response in the bronchoalveolar cells. These results suggest that this approach may be useful in describing the initial stages of RAO development in the horse.

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    ABSTRACT: The goal of the present study was to investigate mRNA expression levels of several cytokines and inflammatory mediators in broncho-alveolar lavage (BAL) fluid and respiratory epithelium in recurrent airway obstruction (RAO)-affected horses. RAO, also called heaves, is a common, performance-limiting, equine respiratory disease with clinical signs and pathophysiological similarities to human asthma, and characterized by bronchospasm, neutrophilic infiltration and increased mucus in the airways. Six RAO-affected horses were examined twice within 15 days and seven clinically healthy horses were examined for comparison. Quantitative real-time RT-PCR was used to assess mRNA expression of the inflammatory mediators IL-1β, IL-6, IL-8, IL-13, IL-17, TNFα, INFγ, TGFβ1, NFκ-β and TRL4 in bronchial biopsies and in BAL fluid. Gene expression levels were then compared with clinical signs, endoscopic examination, complete blood cell count, cytology of BAL fluid, histological examination of bronchial tissue and bacteriological and mycological examinations. Expression of IL1β, IL8, TLR4, TNFα, TGFβ1 and NFkβ transcripts was significantly up-regulated in RAO-affected compared to healthy horses. A similar trend, albeit not significant, was showed for IL17 and INFγ. A highly significant correlation was observed among IL-1β, IL8, TGFβ1, NFkβ, TRL4, and INFγ expression patterns as well as between expression levels of these genes and clinical parameters. In the present study, the comparison between clinically healthy and RAO-affected horses gave new insights on the cytokine expression in equine health and disease status. The identification of cytokines implicated in the pathogenesis of RAO may contribute to the diagnosis and treatment of this disease.
    Veterinary Immunology and Immunopathology 10/2013; DOI:10.1016/j.vetimm.2013.09.020 · 1.75 Impact Factor
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    ABSTRACT: Animal models have been developed to investigate specific components of asthmatic airway inflamma-tion, hyper-responsiveness or remodelling. However, all of these aspects are rarely observed in the same animal. Heaves is a naturally occurring disease of horses that combines these features. It is character-ized by stable dust-induced inflammation, broncho-spasm and remodelling. The evaluation of horses during well-controlled natural antigen exposure and avoidance in experimental settings allows the study of disease mechanisms in the asymptomatic and symp-tomatic stages, an approach rarely feasible in humans. Also, the disease can be followed over several years to observe the cumulative effect of repeated epi-sodes of clinical exacerbation or to evaluate long-term treatment, contrasting most murine asthma models. This model has shown complex gene and environment interactions, the involvement of both innate and adaptive responses to inflammation, and the contri-bution of bronchospasm and tissue remodelling to airway obstruction, all occurring in a natural setting. Similarities with the human asthmatic airways are well described and the model is currently being used to evaluate airway remodelling and its reversibility in ways that are not possible in people for ethical reasons. Tools including antibodies, recombinant pro-teins or gene arrays, as well as methods for sampling tissues and assessing lung function in the horse are constantly evolving to facilitate the study of this animal model. Research perspectives that can be relevant to asthma include the role of neutrophils in airway inflammation and their response to corticos-teroids, systemic response to pulmonary inflamma-tion, and maintaining athletic capacities with early intervention.
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