Chlamydia pneumoniae has recently been associated with atherosclerotic lesions in coronary arteries. To investigate the biological basis for the dissemination and proliferation of this organism in such lesions, the in vitro growth of C. pneumoniae was studied in two macrophage cell lines, peripheral blood monocyte-derived macrophages, human bronchoalveolar lavage macrophages, several endothelial cell lines, and aortic smooth muscle cells. Five strains of C. pneumoniae were capable of three passages in human U937 macrophages and in murine RAW 246.7 macrophages. Titers were suppressed in both macrophage types with each passage, as compared with growth titers in HEp-2 cells. Both human bronchoalveolar lavage macrophages and peripheral blood monocyte-derived macrophages were able to inhibit C. pneumoniae after 96 h of growth. Eleven C. pneumoniae strains were capable of replicating in normal human aortic artery-derived endothelial cells, umbilical vein-derived endothelial cells, and pulmonary artery endothelial cells. Infection in human aortic artery smooth muscle cells was also established for 13 strains of C. pneumoniae. The in vitro ability of C. pneumoniae to maintain infections in macrophages, endothelial cells, and aortic smooth muscle cells may provide support for the hypothesis that C. pneumoniae can infect such cells and, when infection is followed by an immune response, may contribute to atheroma formation in vivo. More studies are needed to investigate the complex relationship between lytic infection and persistence and the potential for C. pneumoniae to influence the generation of atheromatous lesions. Chlamydia pneumoniae has been established as an important respiratory pathogen associated with 5 to 10% of communityacquired cases of pneumonia, pharyngitis, bronchitis, and sinusitis (3, 5, 7, 11-14, 25). In addition, C. pneumoniae infection has been associated with asthma, acute chest syndrome of sickle cell anemia, human immunodeficiency virus infection, Guillain-Barré syndrome, endocarditis, and otitis media and with patients with immunosuppressive diseases (1, 4, 8, 16, 17, 26-28). Cases of chronic persistent respiratory infection, in which antibiotic therapy failed to eradicate the organism, have also been reported (18). There is also evidence that C. pneumoniae can be cultured infrequently (2 and 4.5%, respectively) from asymptomatic and selectively healthy individuals (10, 20, 21). More recently, C. pneumoniae has been associated with coronary artery disease (24, 30, 31, 33, 34). The earliest serological association was reported by Saikku et al., who demonstrated an association of increased antibody titers to C. pneumoniae in men with acute myocardial infarction and chronic coronary heart disease (31). In another prospective study, they demonstrated that chronic C. pneumoniae infection may be a risk factor for the development of coronary heart disease (30). In the United States, Thom et al. reported a relationship between antibody to C. pneumoniae and angiographically demonstrated coronary artery di...

An in vitro culture system was used to study the effects of increasing concentrations of human cytokines on the intracellular replication of Chlamydia pneumoniae. HEp-2 cell monolayers, pretreated for 24 h with 200 U of human recombinant gamma interferon (IFN-␥) per ml restricted the intracellular replication of C. pneumoniae. Tumor necrosis factor alpha (TNF-␣; 25 ng/ml) exhibited a synergistic effect with IFN-␥ by reducing the concentration of IFN-␥ necessary to restrict intracellular growth to 100 U/ml. The addition of 200 g of tryptophan per ml significantly reversed the inhibitory effects of IFN-␥ and TNF-␣, suggesting involvement of the indoleamine-2,3-dioxygenase pathway in the restriction process.

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