Asthma animal models

The worldwide incidence, morbidity, and mortality of allergic asthma are increasing. Asthma has become an epidemic, affecting 155 million individuals throughout the world. It is a complex disorder characterized by local and systemic allergic inflammation, mucus hypersecretion, and reversible airway obstruction [88]. The pathogenesis of asthma reflects the activity of cytokines from Th2 cells. Without these cells there is no asthma. Animal models support important roles for the cytokines IL-4, IL-5, and the recent IL-13 [89]. The latter is closely related to IL-4 they both bind to the same IL-4 receptor, to the a-chain of that receptor, particularly. 

Nyce W, Metzger W (1997) DNA antisense therapy for asthma in an animal model. Nature 385(6618) 721-725... 

The antibodies to IL-4 inhibit allergen-induced airway hyperresponsiveness (AHR), globlet cell metaplasia and pulmonary eosinophilia in animal models. Inhibition of IL-4 by soluble IL-4 receptor (SIL-4R, Nuvance) has proven to be very promising in treating asthma. Clinical trials with recombinant SIL-4R administered by a single weekly dose of 3 mg via nebulization have been effective in controlling the symptoms of moderate persistent asthma. 

Many investigators have studied the therapeutic effects of yogurt and LAB commonly used in yogurt production on diseases such as cancer, infection, gastrointestinal disorders, and asthma. Because the immune system is an important contributor to all of these diseases, the immunostimulatory effects of yogurt were studied by several investigators. Most of these studies used animal models few human studies on the immunostimulatory effects of yogurt have been conducted. 

Candidate genes can be selected using a variety of approaches such as literature searches, genes resulting from experiments in animal models, homology searches, and gene expression experiments. Studies testing even dozens of candidates at once exist for many complex diseases cardiovascular disease (83), osteoarthritis (84), and asthma (85) to name a few. 

McClain, S. and Bannon, G.A. 2006. Animal models of food allergy Opportunities and barriers. Curr Allergy Asthma Rep 6 141-144. 

Most of the literature to date on air pollution and asthma has concentrated on acute exacerbations resulting from environmental exposures. The role of environmental irritants in the induction of asthma is much less well understood. Various air pollutants can enhance allergic sensitization in animal models (Gilmour, 1995) and... 

Milk fat contains several compounds that have demonstrated anticancer activity in animal models. The more important ones are rumenic acid, a potent inhibitor of mammary tumorigenesis, sphingomyelin and other sphingolipids that prevent the development of intestinal tumors and butyric acid, which prevents colon and mammary tumor development. Emerging evidence suggests that milk fat can prevent intestinal infections, particularly in children, prevent allergic disorders, such as asthma and improve the level of long-chain co-3 polyunsaturated fatty acids in blood. 

Much inflammation in asthma is thought to be a consequence of the inappropriate accumulation of eosinophils and the subsequent release of their potent proinflammatory arsenal that includes such diverse elements as granule-derived basic proteins, mediators, cytokines, and chemokines (5). Interleukin (lL)-5 is cmcial to the development and release of eosinophils from the bone marrow, their enhanced adhesion to endothelial cells that line the postcapillary venules, and their persistence, activation, and secretion in the tissues. Several animal models of asthma including the use of primates have provided good evidence... 

Good evidence from animal models indicates that a4 1 (VLA ) is a viable drug target for asthma. Monoclonal antibodies (mAb) against the a4 subunit of VLA-4 have proven efficacious in asthma models in five different species. For example, in a mouse model of asthma, intravenously administered anti-a4 mAb eliminated eosinophilia but did not affect AHR. In contrast, when delivered intranasally, the mAb blocked both airway inflammation and AHR (54). The small-molecule VLA-4 antagonist (2S)-3-(4-Dimethylcarbamoyloxyphenyl)-2- ((4R)-5, 5-dimethyl-3-(l-methyl-lH-pyrazole-4sulfonyl)thiazolidine -... 

It has also been reported that airway epithelial cells, in particular those from humans, produce NO during chronic inflammation. WhUe this mediator has been proposed to exert a variety of effects in asthma including those directly involved with development of the symptoms of airways obstruction, our results in the animal models surest that this function may also contribute to eventual limitation of T ceU-mediated airways inflammation via suppression of GM-CSF-induced DC maturation. 

Various studies have also examined animal models of pulmonary inflammation that are representative of primary eosinophil or neutrophil infiltration. Lung inflammation characterized by eosinophil influx has been used as a model of asthma and is not generally associated with lung fibrosis. After several episodes of repeated antigen challange, a subset of Ascaris -sensitive Cynomolgus monkeys developed a persistent eosinophilia and enhanced intercellular adhesion molecule-1 (ICAM-1) expression on pulmonary endothelial and epithelial cells when compared to control animals (Gundel etal., 1991, 1992). 

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