Altered serum levels of IL-33 in patients with advanced systolic chronic heart failure: correlation with oxidative stress.
BACKGROUND
Interleukin-33 (IL-33) has been linked to chronic heart failure (CHF) in animal studies, but data on serum IL-33 levels in human CHF are not available. We analyzed levels of IL-33 in serum, and investigated the possible role of IL-33 in oxidative stress.


METHODS
A total of 191 subjects with advanced systolic CHF (CHF group), 175 patients with pre-existing cardiac diseases but no CHF (non-CHF group), and 177 healthy controls (HC group) were enrolled. Serum levels of IL-33, soluble ST2 (sST2) and N-terminal-pro-brain natriuretic peptide (NT-proBNP), malondialdehyde (MDA) content, erythrocyte superoxide dismutase (eSOD) activity, as well as left ventricular ejection fraction (LVEF), were determined. The exact form of IL-33 in serum was identified. Effects of IL-33 and sST2 on MDA content and SOD activity in angiotensin (Ang II)-stimulated AC16 cells were assessed.


RESULTS
Serum levels of IL-33 and sST2 were elevated in CHF patients, whereas IL-33/sST2 ratios were decreased. In CHF patients, pre-existing cardiac diseases and medications used upon hospital admission did not affect IL-33 concentrations or the IL-33/sST2 ratio. Full-length IL-33, which could not be detected in serum from HC and barely detected in non-CHF patients, was significantly up-regulated in CHF patients. IL-33 levels were positively correlated with markers of CHF severity. IL-33/sST2 ratios were slightly and negatively related to MDA concentrations. IL-33 directly reduced MDA and enhanced SOD activity in Ang II-stimulated AC16 cells, which were greatly attenuated by sST2.


CONCLUSIONS
Serum levels of IL-33, especially the full-length form, were elevated in CHF patients whereas IL-33 bioactivity was reduced. In advanced CHF, IL-33 may exert anti-oxidation effects, which may be overwhelmed by concurrently elevated levels of sST2.
Department of Cardiology, Sun Yat-sen Memory hospital, Sun Yat-sen University, Guangzhou, China.
Hai-Feng
HF
Zhang
Shuang-Lun
SL
Xie
Yang-Xin
YX
Chen
Jing-Ting
JT
Mai
Jing-Feng
JF
Wang
Wa-Li
WL
Zhu
Li-Guang
LG
Zhu
D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013599:Systole
C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins