Telithromycin treatment of chronic Chlamydia pneumoniae infection in C57BL/6J mice.
Chronic Chlamydia pneumoniae infections have been associated with atherosclerosis, but clear knowledge about how these infections should be treated is lacking. We studied the effect of a new ketolide antibiotic, telithromycin, on chronic C. pneumoniae lung infection. Female C57BL/6J mice on a 0.2% cholesterol diet were inoculated intranasally with C. pneumoniae either two or three times every fourth week. Telithromycin was given to the mice subcutaneously at 75 mg/kg of body weight once daily for 5 or 10 days, starting at 3 days after the last inoculation. Samples were taken at 4 and 12 weeks after the last inoculation. The presence of C. pneumoniae DNA in lung tissue was demonstrated by PCR and the detection of lipid accumulation in the aortic sinus by Oil-Red-O staining. C. pneumoniae DNA positivity and inflammatory reactions in the lung tissue of the mice inoculated twice were significantly affected by treatment after both inoculations or only after the second inoculation at 12 weeks. Intimal lipid accumulation in the aortic sinus was also slightly but significantly less abundant in the mice treated after both inoculations compared to the levels in those treated only after the second inoculation for 10 days (geometric means, 823 and 4,324 microm(2), respectively; P = 0.033). No differences between the infected, untreated controls and the group inoculated three times and treated for 5 days were seen. We conclude that telithromycin is effective in preventing the development of chronic C. pneumoniae infection and intimal lipid accumulation in C56BL/6J mice when the treatment is given after each inoculation.
Törmäkangas
Liisa
L
National Public Health Institute, P.O. Box 310, FIN-90101 Oulu, Finland. liisa.tormakangas@ktl.fi
Alakärppä
Hannu
H
David
Denise Bem
DB
Leinonen
Maija
M
Saikku
Pekka
P
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000473:pathology; D016993:Chlamydophila pneumoniae; D002908:Chronic Disease; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D048628:Ketolides / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012850:Sinus of Valsalva / Q000473:pathology
D048628:Ketolides; D004247:DNA; C106791:telithromycin