Circulating cytokine levels in mice with heart failure are etiology dependent

Vistnes M, Wahre A, Nygard S, Sjaastad I, Andersson KB, Husberg C, Christensen G. Circulating cytokine levels in mice with heart failure are etiology dependent. J Appl Physiol 108: 1357-1364, 2010. First published March 11, 2010; doi:10.1152/japplphysiol.01084.2009.-Objectives: The aim of this study was to examine whether alterations in circulating cytokine levels are dependent on the etiology of myocardial hypertrophy and heart failure (HF). Background: Several heart diseases are associated with altered levels of circulating cytokines. Cytokines are regarded as possible therapeutic targets or biomarkers, but such approaches are currently not in clinical use. If alterations in circulating cytokines are etiology dependent, this should be taken into consideration when using cytokines as disease markers and therapeutic targets. Methods: The serum levels of 25 cytokines were quantified with Luminex and/or ELISA in four murine models of heart disease: banding of the ascending aorta (AB) or the pulmonary artery (PB), myocardial infarction (MI), and a cardiomyopathy model with inducible cardiomyocyte-specific knockout of the sarco(endo)plasmatic reticulum Ca(2+) -ATPase (SERCA2KO). Results: No increase in circulating cytokine levels were found in mice 1 wk after AB, although substantial myocardial hypertrophy was present. After 1 wk of MI, only interleukin (IL)-18 was increased. In the SERCA2KO mice with HF, circulating levels of IL-1 alpha, IL-2, IL-3, IL-6, IL-9, IL-10, IL12p40, eotaxin, granulocyte-colony stimulating factor (G-CSF), interferon-gamma, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta were increased, and in mice with PB, IL-1 alpha, IL-6, G-CSF, and monokine induced by gamma-interferon showed elevated levels. Conclusions: Serum levels of cytokines in mice with HF vary depending on the etiology. Increased serum levels of several cytokines were found in models with increased right ventricular afterload, suggesting that the cytokine responses result primarily from systemic congestion.