ANIMAL MODELS OF PULMONARY INFECTION IN THE COMPROMISED HOST: Potential Usefulness for Studying Health Effects of Inhaled Particles

Pulmonary infection leading to pneumonia is a significant cause of morbidity and mortality worldwide. Airborne particles have been associated with pneumonia through epidemiological research, but the mechanisms by which particles affect the incidence of pneumonia are not well established. The purpose of this review is to examine the potential of animal models to improve our understanding of the mechanisms by which inhaled particles might affect the incidence and resolution of pulmonary infection. The pathogenesis of pneumonia in most animal models differs from that in humans because humans frequently have underlying diseases that predispose them to infection with relatively low doses of pathogens. Normal, healthy animals lack the underlying pathology often found in humans and clear bacteria and viruses rapidly from their lungs. To overcome this, animals are administered large inocula of pathogens, are treated with agents that cause mucosal lesions, or are treated with immunosuppressive drugs. Alternatively, pathogenic bacteria are protected from phagocytosis by encasing them in agar. No one animal model will replicate a human disease in its entirety, and the choice of model depends upon how well the animal infection mimics the particular human response being examined. The advantages and disadvantages of animal models in current use for bacterial and viral infections important in the etiology of human pneumonia are reviewed in detail. Considerable data indicate that prior exposure to particles compromises the ability of experimental animals to resolve a subsequent infection. In addition, information is available on the effects of particle exposure on various portions of respiratory defense including phagocytic function, ciliary movement, inflammation, and antibody response in the absence of infection. In contrast, little research to date has examined the consequences of particle exposure on the host defense mechanisms of animals already infected or on their ability to resolve their infection.