Animal models of asthma

Abstract

SummaryAnimal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma.

EGF receptor activation during allergic sensitization affects IL‐6‐induced T‐cell influx to airways in a rat model of asthma

“…RNA yield and quality were measured with a spectrophotometer and RNA integrity was analyzed with an automated electrophoresis system (Experion, Bio-Rad Laboratories, Hercules, CA, USA). Strand cDNA was made in a 20 mL reaction, using of 1 mg of total RNA as a template, Oligo(dT) [12][13][14][15][16][17][18] primer, dNTP mix, RNaseOUT, and SuperScript II Reverse Transcriptase (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions.…”

“…A recent publication has suggested a role for amphiregulin, an EGFR ligand, in Th2-cell differentiation in the mouse [15]. Therefore, it is possible that EGFR signaling may be important during the sensitization phase of the immune response to allergen and may affect airway inflammation and airway responsiveness by altering the function of immune cells including lymphocytes.The BN rat model of asthma has been widely used [4,16] as it develops high levels of IgE upon sensitization [17] and has typical Th2 inflammation, early-and late-phase airway responses and AHR after allergen challenge [18]. In the current study, we hypothesized that the inhibition of EGFR signaling by the selective EGFR-TK inhibitor AG1478 given at the time of allergic sensitization was capable of modulating immune reactions in the BN rat.…”

“…The BN rat model of asthma has been widely used [4,16] as it develops high levels of IgE upon sensitization [17] and has typical Th2 inflammation, early-and late-phase airway responses and AHR after allergen challenge [18]. In the current study, we hypothesized that the inhibition of EGFR signaling by the selective EGFR-TK inhibitor AG1478 given at the time of allergic sensitization was capable of modulating immune reactions in the BN rat.…”

Characterization of a novel model incorporating airway epithelial damage and related fibrosis to the pathogenesis of asthma

“…Female Balb/c wild-type mice have been shown to be more prone to a Th2 response and undergo higher airway reactivity (in response to allergens) compared with their male counterparts and other commonly used murine strains, 18,19 and as such have been used extensively in chronic AAD models. 20,21 All experimental procedures were performed according to the regulations approved by the Monash University Animal Ethics Committee, which adheres to the Australian Guidelines for the Care and Use of Laboratory Animal for Scientific Purposes.…”

Revisão Sistemática Sobre Modelos Experimentais De Asma Aguda E Crônica Induzidos Com Extrato De Ácaro Da Poeira Doméstica

“…Por ser uma doença muito complexa e de grande prevalência, a asma alérgica tem sido muito estudada através de experimentos com camundongos. Os camundongos são os animais mais populares para estudos experimentais com asma, pois são de baixo custo, facilmente sensibilizados por alérgenos e demonstram hiper-responsividade das vias aéreas 11 . Assim, vários protocolos distintos têm sido publicados com modelos murinos de HDM.…”