Apolipoprotein E-deficient mice develop an anti-Chlamydophila pneumoniae T helper 2 response and resist vascular infection.
Atherosclerosis: Methodological Considerations To the Editor: In contrast to several previously published studies,1–3 the one by Caligiuri et al4 failed to observe an accelerating effect of Chlamydia pneumoniae infection on atherosclerotic lesion development in apolipoprotein E–deficient mice. There are several critical differences in experimental design that likely account for these contrasting observations. In their initial studies, Caligiuri et al4 administered a single, nonpurified, low titer dose of C pneumoniae (1 10 ifu/mouse). This method is in contrast to the other studies where multiple inoculations of higher titers of purified C pneumoniae (5 10 to 3x10 ifu/mouse) were administered at intervals of 1 or 2 weeks. We have previously demonstrated that a single inoculation in animals at 8 weeks of age does not produce a sustained infection in the aorta, whereas multiple inoculations lead to a sustained infection for up to 20 weeks.5 The age of the animals at the time of inoculation, the interval between inoculations, and the length of time post-inoculation are also critical elements for accelerating lesion development.1-3 For example, we have demonstrated that there is a more significant increase in lesion area in the aortic arch in animals at 6 weeks as compared with 10 weeks after inoculation.1 In the study by Caligiuri et al,4 the combination of a single inoculation administered to 6to 8-week-old mice, coupled with the prolonged duration post-inoculation (22 weeks), may have accounted for their failure to observe an acceleration of lesion development. Additionally, in the second arm of their study, a “booster” inoculation was administered at 18 weeks. This dose was likely administered much too late to have any contributory effect on lesion development. It is clear from serological evidence that humans are subject to repeat infections throughout life. At present, the time intervals of infection that best simulate the impact of C pneumoniae on cardiovascular disease end points in animal models have not been defined. However, previous studies have uniformly shown that induction of a persistent infection in the artery wall is a critical factor for enabling C pneumoniae to promote atherosclerosis.