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J Am Coll Cardiol, 2001; 38:187-193
© 2001 by the American College of Cardiology Foundation
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Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure—modulatory effect of intravenous immunoglobulin

Jan K. Damås, MD* {dagger}, Lars Gullestad, MD, PhD*, Halfdan Aass, MD, PhD*, Svein Simonsen, MD, PhD*, Jan G. Fjeld, MD, PhD{ddagger}, Lisbeth Wikeby, RN* {dagger}, Thor Ueland, BS{dagger} §, Hans G. Eiken, PhD{dagger}, Stig S. Frøland, MD, PhD{dagger} || and P.ål Aukrust, MD, PhD{dagger} ||

* Department of Cardiology, Medical Department, University of Oslo, The National Hospital, Oslo, Norway
{dagger} Research Institute for Internal Medicine, Medical Department, University of Oslo, The National Hospital, Oslo, Norway
{ddagger} Section of Nuclear Medicine, Medical Department, University of Oslo, The National Hospital, Oslo, Norway
§ Section of Endocrinology, Medical Department, University of Oslo, The National Hospital, Oslo, Norway
MSD-Cardiovascular Research Center, Medical Department, University of Oslo, The National Hospital, Oslo, Norway
|| Section of Clinical Immunology and Infectious Diseases, Medical Department, University of Oslo, The National Hospital, Oslo, Norway



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Figure 1 Representative RNase protection assay (RPA) (A) and relative messenger ribonucleic acid (mRNA) levels (B) of chemokines in mononuclear blood cells (MNCs) from 20 patients with chronic heart failure (CHF) and 10 healthy control subjects (CTR). Horizontal lines indicate mean values. GAPDH = glyceraldehyde-3-phosphate dehydrogenase; I-309 = inducible-309; IL-8 = interleukin-8; IP-10 = interferon {gamma} inducible protein-10; MCP-1 = monocyte chemoattractant protein-1; MIP-1{alpha} = macrophage inflammatory protein-1{alpha}; MIP-1ß = macrophage inflammatory protein-1ß; RANTES = regulated upon activation, normally T cell expressed and secreted; rpL32 = ribosomal protein L32.

 


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Figure 2 Relative messenger ribonucleic acid (mRNA) levels of CC chemokine receptor (A) and CXC chemokine receptor (B) in mononuclear blood cells (MNCs) from 20 patients with chronic heart failure (CHF) and 10 healthy control subjects (CTR). Horizontal lines indicate mean values. rpL32 = ribosomal protein L32.

 


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Figure 3 Relative messenger ribonucleic acid (mRNA) levels of macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) (A), macrophage inflammatory protein-1ß (MIP-1ß) (B) and interleukin-8 (IL-8) (C) in mononuclear blood cells from 20 patients with chronic heart failure before and after six months (mo) of treatment with intravenous immunoglobulin (IVIg) (n = 10) or placebo (n = 10). As for MIP-1{alpha} (p < 0.01) and MIP-1ß (p < 0.01), there were also differences in changes between the two groups. Horizontal lines indicate mean values; n.s. = not significant. rpL32 = ribosomal protein L32.

 


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Figure 4 Plasma levels of macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) (A), macrophage inflammatory protein-1ß (MIP-1ß) (B) and interleukin-8 (IL-8) (C), given as the percent change from baseline (MIP-1{alpha}: 25.2 ± 2.0 pg/ml; MIP-1ß: 93.4 ± 4.5 pg/ml; IL-8: 22.8 ± 1.8 pg/ml), in 20 patients with chronic heart failure before and at different time points after initiating treatment with intravenous immunoglobulin (n = 10; solid circles) or placebo (n = 10; open circles). Data are given as the mean value ± SEM. *p < 0.05; **p < 0.01 versus baseline; #p < 0.05 when comparing changes between intravenous immunoglobulin and placebo.

 


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Figure 5 Relative messenger ribonucleic acid (mRNA) levels of chemokine receptor (CCR) 1 (A), CCR5 (B) and CXCR1 (C) in mononuclear blood cells from 20 patients with chronic heart failure before and after six months (mo) of treatment with intravenous immunoglobulin (IVIg) (n = 10) or placebo (n = 10). As for CCR1 (p < 0.001) and CCR5 (p < 0.01), there were also differences in changes between the two groups. Horizontal lines indicate mean values; n.s. = not significant. rpL32 = ribosomal protein L32.

 


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Figure 6 Correlation between absolute change in left ventricular ejection fraction (LVEF) (%), as assessed by electrocardiographically synchronized, gated radionuclide ventriculography at rest, and absolute change in messenger ribonucleic acid (mRNA) levels of macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) in mononuclear blood cells from 10 patients with chronic heart failure receiving intravenous immunoglobulin for six months (mo). rpL32 = ribosomal protein L32.

 




 
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