Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.
ABSTRACT In horses prone to developing recurrent airway obstruction (RAO), we tested the hypotheses that the cytokine profile in the bronchoalveolar lavage (BAL) cells of affected horses would reflect a polarized Th-2 response; that cytokine and chemokine alterations would occur within 24 h of allergen exposure; and that allergen exposure would induce alterations in the expression of the transcription factor t-bet (t-box-expressed in T-cells). The expression levels of interleukin-4 (IL-4), IL-13, Interferon-gamma (IFN-gamma), t-bet, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) were measured in BAL cells obtained from control and RAO-susceptible horses during an asymptomatic phase and at 24 h and 5 weeks post-stabling and hay exposure. At each sampling time, BAL neutrophil percentages in the RAO-group exceeded controls. In the RAO-group, only IL-13 expression was decreased 2-fold during the asymptomatic phase. No differences in cytokine or chemokine expression were detected during the acute exposure phase. During the chronic phase, IFN-gamma and IL-8 expression levels were 2.5- and 3-fold greater, respectively, in the RAO-group. No other differences in gene expression were detected. We conclude that the cytokine profile of the airway cells does not reflect a polarized Th-2 response; that increases in IFN-gamma result from a t-bet independent pathway and that chemokines from epithelial or interstitial cells may contribute to early neutrophil influx.
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ABSTRACT: Diseases of the lower airways represent some of the most common conditions affecting horses of all ages, but the type and severity tends to follow the horses' age. The age-related dysregulation of pro-inflammatory cytokines may, in part contribute to the development of the diseases. Therefore, we hypothesize that the expression of pro-inflammatory cytokines increases with age. Peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells from clinically healthy horses of different ages were used for the investigation. The cells were stimulated and the production of IFN-γ and TNF-α measured using flow cytometry. The frequency of IFN-γ producing lymphocytes in both BAL and PBMCs from old horses was significantly increased compared to the young horses. The age-related increase of TNF-α production was also found in PBMCs but not in BAL cells. In conclusion, the productions of certain pro-inflammatory cytokine are age-associated. This age-associated increase of pro-inflammatory cytokines production may be a co-factor for the pathogenesis of equine airway diseases.Developmental and comparative immunology 12/2012; · 3.29 Impact Factor
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ABSTRACT: Animal models have been developed to investigate specific components of asthmatic airway inflammation, 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 characterized by stable dust-induced inflammation, bronchospasm 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 symptomatic stages, an approach rarely feasible in humans. Also, the disease can be followed over several years to observe the cumulative effect of repeated episodes 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 contribution 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 proteins 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 corticosteroids, systemic response to pulmonary inflammation, and maintaining athletic capacities with early intervention.Respirology 08/2011; 16(7):1027-46. · 2.78 Impact Factor
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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; · 1.88 Impact Factor