CLINICAL RESEARCH: CORONARY ARTERY DISEASE
Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease
Stephan Fichtlscherer, MD*,*,
Susanne Breuer, MD*,
Christopher Heeschen, MD*,
Stefanie Dimmeler, PhD* and
Andreas M. Zeiher, MD*
* Department of Internal Medicine IV, Division of Cardiology, Johann W. Goethe University, Frankfurt, Germany
Manuscript received September 26, 2003;
revised manuscript received February 4, 2004,
accepted February 10, 2004.
* Reprint requests and correspondence: Dr. Stephan Fichtlscherer, Department of Internal Medicine IV, Division of Cardiology, J. W. Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
fichtlscherer{at}em.uni-frankfurt.de
OBJECTIVES: Because the endothelium is a major target for inflammatory cytokines, we investigated whether elevated interleukin (IL)-10 serum levels are associated with improved endothelial vasoreactivity in patients with coronary artery disease (CAD).
BACKGROUND: Chronic inflammation plays a pivotal role in the progression of atherosclerosis. Interleukin-10 is an anti-inflammatory cytokine that exerts important protective effects on atherosclerotic lesion development in experimental animals.
METHODS: Vasoreactivity was assessed in 65 male patients with documented CAD by measuring endothelium-dependent (acetylcholine [ACh] 10 to 50 µg/min) and endothelium-independent (sodium nitroprusside [SNP] 2 to 8 µg/min) forearm blood flow (FBF) responses using venous occlusion plethysmography.
RESULTS: Serum levels of IL-10 were significantly correlated with ACh-induced FBF responses (r = 0.31, p < 0.02), but not with SNP responses. Importantly, if IL-10 serum levels were increased in patients with elevated C-reactive protein (CRP) levels, no impairment of ACh-stimulated FBF response was observed. On multivariate analysis, including low-density lipoprotein cholesterol, smoking, hypertension, diabetes, clinical status of the patients, and statin and/or angiotensin-converting enzyme inhibitor treatment, only IL-10 (p < 0.02) and CRP serum levels (p < 0.02) were significant independent predictors of ACh-induced FBF responses.
CONCLUSIONS: Thus, increased IL-10 serum levels are associated with improved systemic endothelial vasoreactivity in patients with elevated CRP serum levels, demonstrating that the balance between pro- and anti-inflammatory mediators is a major determinant of endothelial function in patients with CAD.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | ACh | = acetylcholine | | ACS | = acute coronary syndrome | | CAD | = coronary artery disease | | CRP | = C-reactive protein | | FBF | = forearm blood flow | | HDL | = high-density lipoprotein | | IL | = interleukin | | LDL | = low-density lipoprotein | | NO(S) | = nitric oxide (synthase) | | SNP | = sodium nitroprusside |
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