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Recurrent airway obstruction (RAO) in horses is characterized by IFN-G and IL-8 production in bronchoalveolar lavage cells

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Veterinary Immunology and Immunopathology (Impact Factor: 1.75). 12/2003; 96(1-2):83-91. DOI: 10.1016/S0165-2427(03)00142-9
Source: PubMed

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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    • "Recurrent airway obstruction is characterised by a hypersensitivity reaction to inhaled allergens that can affect genetically predisposed horses confined for long periods in stalls without proper ventilation and fed hay or other products with excessive chaff (Woods et al 1993, Ainsworth et al 2003, Radostits et al 2007, Gerber et al 2009). The exposure of susceptible horses to hay and straw containing dust can initiate inflammation in the lower airways (Fairbairn et al 1993). "
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    • "Several studies have investigated the role of cytokines in RAO, with many diverging theories being proposed (Ainsworth et al., 2003; Cordeau et al., 2004). Before the pathogenesis of age-related diseases , like RAO, can be better understood, there is a need to more fully characterize the immunosenescence of the equine immune system, also, the possibility that age-related changes in immunity or adaptation maybe organ-specific should be considered. "
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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.
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    • "There is some controversy regarding the role of T helper cell subsets and their cytokines in the pathogenesis of RAO. Increased expression of Th2 cytokines IL-4 and IL-5 in RAO-affected horses has been observed by some authors (Lavoie et al., 2001; Cordeau et al., 2004), other studies found increased expression of both Th1 and Th2 cytokines in RAO-affected horses (Giguère et al., 2002), and yet others found no differences in expression of Th2 cytokines between healthy and RAO-affected horses (Ainsworth et al., 2003). Possible explanation for these discrepancies might be the differences in study designs and in the use of different methods of detection. "
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    ABSTRACT: Thymic stromal lymphopoietin (TSLP) is a cytokine involved in lymphocyte development. In humans and mice, TSLP drives the differentiation of T helper 2 (Th2) cells and the development of allergic inflammation. The equine TSLP gene has been previously identified and characterized, but its role in the pathogenesis of equine allergic diseases is not known. Our objective was to assess the expression of TSLP in bronchoalveolar lavage (BAL) cells and in primary bronchial epithelial cells (BEC) isolated from horses with recurrent airway obstruction (RAO). RNA was isolated from BAL cells sampled from clinical cases of RAO (n=8) and from control horses (n=12). Furthermore, BAL samples were taken from an additional group of 8 RAO-susceptible and 8 control horses when on pasture (remission) and after 30 days of exposure to moldy hay (exacerbation). In order to study epithelial cells as a potential source of TSLP, cultures of primary bronchial epithelial cells (BEC) were established from 6 RAO-affected and 6 healthy horses and stimulated in vitro with hay dust solution (HDS). Expression of TSLP mRNA was assessed by quantitative real-time RT-PCR (qPCR). Clinical RAO-cases had higher TSLP expression in BAL than control horses (p<0.05). In an experimental group of horses there was no difference between healthy and susceptible horses in remission, whereas after 30-day experimental exposure to moldy hay, all susceptible horses upregulated TSLP expression in BAL (p=0.008, average 6.36-fold increase), whereas in healthy horses there was no significant increase in TSLP expression. BEC generated both from healthy and RAO-affected horses strongly upregulated TSLP expression after 6 h stimulation with HDS, which identifies epithelial cells as potential sources of TSLP in RAO. Finding of increased TSLP expression by BAL cells of RAO-affected horses is in agreement with the contribution of Th2-driven allergic inflammation in the pathogenesis of RAO.
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