The acute phase reactant response to respiratory infection with Chlamydia pneumoniae: implications for the pathogenesis of atherosclerosis.
The acute phase response to Chlamydia pneumoniae infection was analyzed over a 72 h period post-infection in C57BL/6J mice. A single intra-nasal inoculation stimulated statistically significant increases in the plasma levels of IL-2, IL-5, IL-6, IL-10, IL-12, GM-CSF, IFN-gamma, and serum amyloid A but not TNF-alpha, IL-1beta, IL-4 and serum amyloid P. There was also a decrease in the activity of the HDL protective enzyme paraoxonase as well as a reduced ability of HDL to prevent oxidation of palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine by hydroperoxyoctadecadienoic acid at 48 and 72 h post-infection. To determine whether the C. pneumoniae induced acute phase response had any effect on atherosclerotic plaque stability, we measured the frequency of intra-plaque hemorrhage as a marker of plaque disruption in the innominate arteries of apolipoprotein E deficient mice at 29-30 weeks and 1.5-2.0 years of age. There was an increased frequency of intra-plaque hemorrhage only in the older mice infected with the live organism (8/14) as compared to mice treated with killed C. pneumoniae (2/11) or sham inoculated with PBS (2/12). These results suggest that acute phase reactant proteins produced in response to pulmonary infection with C. pneumoniae may contribute to the progression and destabilization of atherosclerotic lesions.
Campbell
Lee Ann
LA
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA.
Yaraei
Kambiz
K
Van Lenten
Brian
B
Chait
Alan
A
Blessing
Erwin
E
Kuo
Cho-Chou
CC
Nosaka
Tadayoshi
T
Ricks
Jerry
J
Rosenfeld
Michael E
ME
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D023521:Chlamydophila Infections / Q000150:complications* / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000276:immunology* / Q000472:pathogenicity*; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000150:complications* / Q000276:immunology
D000209:Acute-Phase Proteins