Value of animal models for Chlamydia pneumoniae-related atherosclerosis

Chlamydia pneumoniae is strongly implicated in the pathogenesis of atherosclerosis in human beings. Animal models are important to help establish causality, to understand the mechanism of infection induced atherogenesis, to examine interaction of other factors or variables, to explore treatment regimens and their efficacy, and to help develop a vaccine for prevention. To date, the rabbit model is the only animal model shown to develop de novo atherosclerotic changes with C pneumoniae infection. However, the mouse model may be useful to show enhancement with other factors such as hypercholesterolemia and to explore pathogenic mechanisms. In our studies, we have shown that C pneumoniae respiratory infection in the rabbit results in early atherosclerotic changes in 26% with single inoculation and in 35% after triple inoculation, but sham infection or infection with Mycoplasma pneumoniae does not result in similar changes. Early treatment (5 days after inoculation) with 30 mg/kg per day azithromycin once every 6 days was 87% effective in preventing atherosclerotic changes, but delayed treatment (6 weeks after inoculation) was ineffective. Further studies are needed with longer or more aggressive regimens or possible combination of agents to determine whether it is possible to reverse preformed lesions. An effective vaccine for prevention of C pneumoniae -induced pneumonia and possibly atherosclerotic lesions in human beings would have tremendous application and would circumvent the shortcomings of antibiotic therapy.