title: Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model.
abstract: BACKGROUND
  Chlamydia pneumoniae infection has been associated with atherosclerosis by serological studies and detection of bacterial antigen within plaque. We sought to evaluate a possible causal role in an animal model.
  
  
  RESULTS
  Thirty New Zealand White rabbits were given three separate intranasal inoculations of either C pneumoniae (n = 20) or saline (n = 10) at 3-week intervals and fed chow enriched with a small amount (0.25%) of cholesterol. Immediately after the final inoculation, infected and control rabbits were randomized and begun on a 7-week course of azithromycin or no therapy. Three months after the final inoculation, rabbits were euthanatized and sections of thoracic aortas were blindly evaluated microscopically for maximal intimal thickness (MIT), percentage of luminal circumference involved (PLCI), and plaque area index (PAI) of atherosclerosis. Vascular chlamydial antigen was assessed by direct immunofluorescence. MIT differed among treatment groups (P=.009), showing an increase in infected rabbits (0.55 mm; SE = 0.15 mm) compared with uninfected controls (0.16 mm; SE = 0.06 mm) and with infected rabbits receiving antibiotics (0.20 mm; SE = 0.03 mm) (both P<.025), whereas MIT in infected/treated versus control rabbits did not differ. PLCI also tended to differ (P<.1) and PAI differed significantly (P<.01) among groups with a similar pattern. Chlamydial antigen was detected in 2 untreated, 3 treated, and 0 control animals.
  
  
  CONCLUSIONS
  Intranasal C pneumoniae infection accelerates intimal thickening in rabbits given a modestly cholesterol-enhanced diet. In addition, weekly treatment with azithromycin after infectious exposure prevents accelerated intimal thickening. These findings strengthen the etiologic link between C pneumoniae and atherosclerosis and should stimulate additional animal and human studies, including clinical antibiotic trials.
authors.affiliation: University of Utah, LDS Hospital, Salt Lake City 84143, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Muhlestein
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: E H
authors.initials: EH
authors.lastname: Hammond
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: S
authors.initials: S
authors.lastname: Trehan
authors.forename: E P
authors.initials: EP
authors.lastname: Schwobe
authors.forename: J F
authors.initials: JF
authors.lastname: Carlquist
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000032:analysis; D001011:Aorta / Q000382:microbiology / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D017963:Azithromycin / Q000627:therapeutic use*; D002690:Chlamydia Infections / Q000150:complications* / Q000188:drug therapy; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D017963:Azithromycin