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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2648.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Chlamydia pneumoniae Burden in Carotid Arteries Is Associated With Upregulation of Plaque Interleukin-6 and Elevated C-Reactive Protein in Serum

S. Claiborne Johnston; Hui Zhang; Louis M. Messina; Michael T. Lawton; Deborah Dean

From the Department of Neurology (S.C.J., M.T.L.), Division of Vascular Surgery, Department of Surgery (L.M.M.), and Department of Medicine (D.D.), University of California, San Francisco; and Children’s Hospital Oakland Research Institute (H.Z., D.D.), California.

Correspondence to Deborah Dean, MD, MPH, Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, CA 94960. E-mail ddean{at}chori.org

Objective— Chlamydia pneumoniae (Cpn) infection of vascular smooth muscle cells increases interleukin-6 (IL-6) secretion in vitro. In vivo, IL-6 stimulates liver C-reactive protein (CRP) production. Because serum levels of IL-6 and CRP are independent risk factors for stroke and myocardial infarction (MI), we investigated whether Cpn burden in carotid plaques might provide a link between plaque IL-6 expression and elevated serum levels of IL-6 and CRP.

Methods and Results— Consecutive patients undergoing elective carotid endarterectomy were studied. Serum levels of CRP and IL-6 were measured before surgery. Immunohistochemistry and real-time quantitative (k)RT-PCR were used to detect Cpn and the expression of IL-6 within carotid plaques. Cpn mRNA was present in 19 (37%) of 51 patients, suggesting viable infections. These patients had evidence for infection by PCR and immunohistochemistry. The Cpn burden, measured by real-time quantitative (k)-PCR using the number of organisms normalized against the number of eukaryotic cells in the tissue, was associated with plaque expression of IL-6 (Spearman R=0.55; P<0.0001), which was associated with serum levels of IL-6 (R=0.56; P<0.0001) and CRP (R=0.80; P<0.0001).

Conclusions— IL-6 secretion in atherosclerotic plaques infected with Cpn could explain elevated serum inflammatory markers in individuals at risk for stroke and MI.

Serum interleukin-6 (IL-6) and C-reactive protein (CRP) are risk factors for stroke. Carotid plaque Chlamydia pneumoniae (Cpn) burden may contribute to these factors. Burden was significantly associated with IL-6 plaque expression, which was associated with serum IL-6 and CRP. Cpn is associated with inflammation and atherogenesis via upregulation of local and systemic inflammatory markers.

Key Words: inflammatory markers • carotid atherosclerosis • IL-6 • Chlamydia pneumoniae • risk factors

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