Chlamydia pneumoniae antigens facilitate experimental aortic dilatation: prevention with azithromycin.
OBJECTIVE
The purpose of this study was to investigate whether Chlamydia pneumoniae (live, antigens, or polysaccharide) cause abdominal aortic aneurysm in a susceptible animal host with appropriate drug reversal.


METHODS
At laparotomy, preparations of C pneumoniae (live, formalin-inactivated, and heat-inactivated) in calcium chloride were applied to the adventitial surface of the abdominal aorta of rabbits fed a cholesterol-enriched diet. Aortic diameter was measured with ultrasonography. After 3 weeks, immunohistochemistry was used to detect aortic C pneumoniae and macrophages. Presence of C pneumoniae DNA also was assessed.


RESULTS
At high doses (5 x 10(7) organisms) periaortic application of both live and formalin-inactivated preparations resulted in doubling of aortic diameter after 3 weeks, from 2.0 +/- 0.5 mm to 4.3 +/- 1.3 mm (P <.02). C pneumoniae DNA and antigens, together with a heavy macrophage infiltrate, were detected in the dilated aorta. In contrast, periaortic application of heat-inactivated preparations resulted in minimal macrophage influx and aortic dilatation. Treatment of rabbits with azithromycin or carprofen for 10 days after laparotomy abolished the effects of formalin-inactivated C pneumoniae on aortic dilatation. Azithromycin reduced the number of macrophages in the aortic wall more effectively than carprofen.


CONCLUSIONS
Because membrane antigenicity is retained in formalin-inactivated but not heat-inactivated organisms, in this experimental model, chlamydial membrane antigens (rather than live organisms) appear to cause the aneurysmal dilatation and associated macrophage recruitment. Azithromycin is likely to reverse these effects with an antiinflammatory mechanism.
Tambiah
Jeymi
J
Imperial College at Charing Cross, London, United Kingdom.
Powell
Janet T
JT
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000276:immunology*; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy / Q000382:microbiology*; D017963:Azithromycin / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D004269:DNA, Bacterial / Q000378:metabolism; D011817:Rabbits
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000942:Antigens, Bacterial; D002227:Carbazoles; D004269:DNA, Bacterial; D017963:Azithromycin; C007005:carprofen