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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic asthma is a complex chronic inflammatory disease of the airways and its etiology is multifactorial. It involves the recruitment and activation of many inflammatory and structural cells, all of which release inflammatory mediators that result in typical pathological changes of asthma. The features of asthma addressed in this Brown Norway (BN) rat animal model include an analysis of cellular infiltrations in the lung, inflammatory factors in bronchoalveolar lavage (BAL), total immunoglobulin E (IgE) production in serum, and changes in delayed-onset respiratory reactions upon four inhalation challenges (every 2 wk) with polymeric diphenylmethane diisocyanate (MDI) aerosol in two groups of topically sensitized rats. The dependence on the induction-related variables was analyzed by using almost identical surface area doses but different total doses per animal. This regimen caused acute exacerbations of delayed-onset respiratory reactions, for which intensity increased with each challenge. After the fourth challenge BAL neutrophils, lymphocytes, eosinophils, cell counts, protein, and lactate dehydrogenase (LDH) as well as lung weights were significantly increased in sensitized rats relative to naive but challenged controls. Histopathology revealed activated bronchial lymphatic tissue, increased recruitment of inflammatory cells, the beginning of peribronchial/peribronchiolar fibrosis, thickening of alveolar septae, and vascular hypertrophy. Total IgE in serum was significantly increased in sensitized rats. Thus, high-dose topical induction to, and repeated inhalation challenges with, MDI was associated with a marked neutrophilic and a less consistent eosinophilic inflammatory response. With regard to the relative sensitivity of endpoints, those that integrate independently a series of complex physiological events appeared to be most practical to probe positive responses in this animal model. These include postchallenge changes in Penh to identify respiratory responses delayed in onset as well as inflammatory changes in BAL. In summary, this extension of a previous study that used 16 mg MDI/m(3) instead of 39 mg MDI/m(3) that was used in the current study for challenge exposures demonstrates that protocol variables are most critical for the outcome of test. Moreover, the sensitivity of this bioassay to define the typical asthma phenotype can be markedly improved by measurements of respiratory responses delayed in onset rather than immediate in onset. Accordingly, to increase the efficacy of this asthma model moderately irritant concentrations of the hapten have to be used for challenge and at least three to four adequately spaced challenge exposures are required to elicit a typical asthma phenotype.
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PMID:Brown Norway rat asthma model of diphenylmethane 4,4'-diisocyanate. 1619 8

Allergic asthma, an inflammatory disease characterized by the infiltration and activation of various leukocytes, the production of Th2 cytokines and leukotrienes, and atopy, also affects the function of other cell types, causing goblet cell hyperplasia/hypertrophy, increased mucus production/secretion, and airway hyperreactivity. Eosinophilic inflammation is a characteristic feature of human asthma, and recent evidence suggests that eosinophils also play a critical role in T cell trafficking in animal models of asthma. Nicotine is an anti-inflammatory, but the association between smoking and asthma is highly contentious and some report that smoking cessation increases the risk of asthma in ex-smokers. To ascertain the effects of nicotine on allergy/asthma, Brown Norway rats were treated with nicotine and sensitized and challenged with allergens. The results unequivocally show that, even after multiple allergen sensitizations, nicotine dramatically suppresses inflammatory/allergic parameters in the lung including the following: eosinophilic/lymphocytic emigration; mRNA and/or protein expression of the Th2 cytokines/chemokines IL-4, IL-5, IL-13, IL-25, and eotaxin; leukotriene C(4); and total as well as allergen-specific IgE. Although nicotine did not significantly affect hexosaminidase release, IgG, or methacholine-induced airway resistance, it significantly decreased mucus content in bronchoalveolar lavage; interestingly, however, despite the strong suppression of IL-4/IL-13, nicotine significantly increased the intraepithelial-stored mucosubstances and Muc5ac mRNA expression. These results suggest that nicotine modulates allergy/asthma primarily by suppressing eosinophil trafficking and suppressing Th2 cytokine/chemokine responses without reducing goblet cell metaplasia or mucous production and may explain the lower risk of allergic diseases in smokers. To our knowledge this is the first direct evidence that nicotine modulates allergic responses.
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PMID:Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. 1849 Jul 68

Allergic asthma is a pulmonary disease characterized by antigen-induced pulmonary eosinophilia, airway hyperresponsiveness, antigen-specific IgE antibody responses, and broncho-constriction. In attempting to elucidate mechanisms associated with the pathogenesis of this disease, a number of animal models have been developed. The current studies were undertaken to develop a model of allergic asthma model in Brown Norway rats. Unlike the neutrophilic inflammatory response to inhaled particles in most strains of rats, inhalation of antigens in sensitized Brown Norway rats results in a complex cellular response which is characterized by a variety of inflammatory cell types, and is dependent on the time course of inflammatory cell recruitment. In characterizing this ovalbumin-challenge model of allergic asthma, it was important to assess the time course of pulmonary inflammation, cell proliferation, and apoptosis. Male Brown Norway rats were sensitized and boosted with intraperitoneal injections of ovalbumin in aluminum hydroxide on experimental days 1 and 8. On days 15-17, rats were challenged by an inhalation exposure to 5% ovalbumin and were evaluated by bronchoalveolar lavage (BAL) at 24 or 48 h postexposure (PE). Control rats were similarly treated to ovalbumin aerosol exposures; however, these animals had been sensitized and boosted with aluminum hydroxide (minus the ovalbumin). Cell differential evaluations demonstrated that the rats exposed for 3 days/24 h postexposure and for 2 days/ 48 h postexposure produced the greatest numbers of BAL eosinophils and corresponding indicators of pulmonary toxicity. It was interesting to note that earlier exposure time periods (i.e., 1 day/24 h PE) generated a predominantly neutrophilic inflammatory response, while longer exposure/postexposure time periods (i.e., 3 days/48 h) produced a predominant mononuclear inflammatory response. Subsequent studies demonstrated that the 2-day/ 48-h protocol produced the optimum eosinophilic, cytotoxic, cell proliferative, and apoptotic response. Histopathological evaluations demonstrated a chronically active alveolitis and bronchiolitis, characterized by epithelial cell proliferation in the airways and inflammatory cell proliferation in the alveoli. Studies are ongoing to assess the cell types undergoing apoptosis in both the airway and parenchymal regions to fully characterize this model in order to assess its relevance and utility for studying asthma in humans.
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PMID:Time Course of Eosinophilic Recruitment and Pulmonary Toxicity Biomarkers in an Allergic Asthma Model in Brown Norway Rats. 2636 39

Allergic asthma is one of the most common chronic diseases of the airways, however it still remains underdiagnosed and hence undertreated. Therefore, an allergic asthma rat model would be useful to be applied in future therapeutic strategy studies. The aim of the present study was to develop an objective model of allergic asthma in atopic rats that allows the induction and quantification of anaphylactic shock with quantitative variables. Female Brown Norway rats were intraperitoneally sensitized with ovalbumin (OVA), alum and Bordetella pertussis toxin and boosted a week later with OVA in alum. At day 28, all rats received an intranasal challenge with OVA. Anaphylactic response was accurately assessed by changes in motor activity and body temperature. Leukotriene concentration was determined in the bronchoalveolar lavage fluid (BALF), and total and IgE anti-OVA antibodies were quantified in blood and BALF samples. The asthmatic animals' motility and body temperature were reduced after the shock for at least 20 h. The asthmatic animals developed anti-OVA IgE antibodies both in BALF and in serum. These results show an effective and relatively rapid model of allergic asthma in female Brown Norway rats that allows the quantification of the anaphylactic response.
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PMID:Development and Characterization of an Allergic Asthma Rat Model for Interventional Studies. 3248 75