Rapamycin can Inhibit the Development of Chlamydia pneumoniae, which Might Partly Contribute to the Prevention of In-stent Restenosis

Abstract

Rapamycin, an immunosuppressive and antiproliferative drug, is used to prevent neointima formation to reduce the risk of in-stent restenosis with rapamycin eluting-stents. Chronic infection of Chlamydia pneumoniae has been associated with cardiovascular diseases, and could play an important role in the mechanism of restenosis. We examined the effect of rapamycin on the growth of C. pneumoniae in cell cultures. HL cell monolayers were inoculated with C. pneumoniae CWL029 or C. trachomatis L2. Different concentrations of rapamycin were present in the culture medium continuously or for 8-hour periods. After incubation the infected cells were repassaged to fresh HL cell monolayers and incubated in the medium without rapamycin. The newborn inclusions from both passages were checked by fluorescent microscope or electron microscope. The presence of 23 microg/ml rapamycin restricted over 90% of the growth of C. pneumoniae. Continuous presence of 11 microg/ml rapamycin inhibited the growth of C. pneumoniae up to 80% and caused smaller inclusions, fewer chlamydial particles and fewer matured EBs. 11 microg/ml rapamycin presented in first passage caused the reduction of C. pneumoniae to 57% at first passage and 24% at second passage. Sufficient rapamycin can inhibit the growth of C. pneumoniae effectively, but it should be applied at the early stage of the chlamydial infections. Rapamycin eluting-stents can induce a high enough local concentration of rapamycin. This provides a possibility for us to suppose that the beneficial effect of rapamycin in preventing in-stent restenosis might partly be explained by its inhibitory effects on the growth of C. pneumoniae.