Circulating cytokine levels in mice with heart failure are etiology dependent.
OBJECTIVE
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 Ca2+-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-1alpha, IL-2, IL-3, IL-6, IL-9, IL-10, IL-12p40, eotaxin, granulocyte-colony stimulating factor (G-CSF), interferon-gamma, monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta were increased, and in mice with PB, IL-1alpha, 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.
Vistnes
Maria
M
Institute for Experimental Medical Research, Oslo University Hospital Ullevål, and Center for Heart Failure Research, University of Oslo, Kirkeveien 166, N-0407 Oslo, Norway. r.m.vistnes@studmed.uio.no
Waehre
Anne
A
Nygård
Ståle
S
Sjaastad
Ivar
I
Andersson
Kristin B
KB
Husberg
Cathrine
C
Christensen
Geir
G
D000818:Animals; D001011:Aorta / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D006332:Cardiomegaly / Q000276:immunology; D009202:Cardiomyopathies / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006333:Heart Failure / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications* / Q000276:immunology; D011651:Pulmonary Artery / Q000601:surgery; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D018497:Ventricular Dysfunction, Right / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right; D017725:Ventricular Pressure
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse