Preclinical animal models of asthma and chronic obstructive pulmonary disease.
Animal models of disease serve a vital function in the search for novel therapeutic approaches. While these systems cannot replicate human disease, they can be used to mimic and investigate mechanisms believed to be central to disease pathogenesis. In this review, we discuss the most relevant and commonly used animal models for asthma and chronic obstructive pulmonary disease (COPD); specifically, models developed for the mouse, rat and guinea pig. Allergens, such as ovalbumin, can be used to induce an IgE-dependent response characterized by early- and late-phase bronchoconstriction, inflammation and airway hyper-responsiveness similar to what occurs in asthmatics. Similarly, elastase and cigarette smoke can be used to replicate steroid-insensitive and progressive inflammation, which leads to lung pathologies that are observed in COPD patients. We also discuss how these models are developing in new ways to more closely reflect the clinical disease. Unfortunately, these models have limitations due to differences in genetics, anatomy and physiology among the species, many of which we have highlighted; however, understanding these differences, careful characterization of these models and parallel in vitro or ex vivo studies using human and relevant animal tissues will overcome some of these issues. In spite of these limitations, as long as studies are designed and interpreted appropriately, in vivo models will continue to be vital for furthering our understanding of disease pathogenesis and for developing new therapies.
Stevenson
Christopher S
CS
Respiratory Pharmacology Group, National Heart and Lung Institute, Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK. c.stevenson@imperial.ac.uk
Belvisi
Maria G
MG