Relevance of animal models for chronic bacterial airway infections in humans.

Abstract

Animal models of chronic bacterial airway infections are limited in relevance to human infection, not only because of limitations present in all animal models (e.g., abnormal sequence of pathologic events, artificial imposition of infection involving large inocula, dissimilar host pharmacokinetic attributes), but especially because underlying disease (chronic obstructive pulmonary disease, or COPD) is usually absent. A major problem in establishing chronic lung infection models is the rapid clearance of bacteria instilled into the drugs; this can be overcome by encasing bacteria into agar beads to restrict phagocytosis. Despite these limitations, animal models based upon agar bead-encased inocula have provided persistent infections resulting in lung pathology and high humoral immune responses similar to that observed in patients with COPD. Such models have illuminated some aspects of the virulence of the bacteria, the involvement of bacterial exoenzymes in promoting lung damage, the potential of vaccination to restrict infectious exacerbations, and the activity of subminimal inhibitory concentrations of antibiotics in reducing lung damage by inhibiting exoenzyme release. Animal models have also shown that anti-inflammatory therapy may be effective in reducing inflammation-associated lung damage. Despite the limitations of chronic lung infection models, they may provide insight into pathologic events and positive therapeutic intervention for lung infections of patients with COPD.