Department of Cardiology, Sun Yat-sen Memory hospital, Sun Yat-sen University, Guangzhou, China.
J Transl Med. 2012 Jun 8;10:120. doi: 10.1186/1479-5876-10-120.
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.
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.
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.
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.
白细胞介素-33 (IL-33) 在动物研究中与慢性心力衰竭 (CHF) 有关，但人类 CHF 血清中 IL-33 水平的数据尚不可用。我们分析了血清中 IL-33 的水平，并研究了 IL-33 在氧化应激中的可能作用。
共纳入 191 例晚期收缩性 CHF 患者（CHF 组）、175 例存在心脏疾病但无 CHF 患者（非 CHF 组）和 177 例健康对照者（HC 组）。测定血清 IL-33、可溶性 ST2（sST2）和 N 末端脑利钠肽前体（NT-proBNP）、丙二醛（MDA）含量、红细胞超氧化物歧化酶（eSOD）活性以及左心室射血分数（LVEF）。确定血清中 IL-33 的具体形式。评估 IL-33 和 sST2 对血管紧张素（Ang II）刺激的 AC16 细胞 MDA 含量和 SOD 活性的影响。
CHF 患者血清中 IL-33 和 sST2 水平升高，而 IL-33/sST2 比值降低。在 CHF 患者中，入院前的基础心脏病和入院时使用的药物并不影响 IL-33 浓度或 IL-33/sST2 比值。在 HC 组血清中无法检测到、在非 CHF 患者中几乎检测不到的全长 IL-33，在 CHF 患者中显著上调。IL-33 水平与 CHF 严重程度标志物呈正相关。IL-33/sST2 比值与 MDA 浓度呈轻度负相关。IL-33 直接降低 Ang II 刺激的 AC16 细胞中的 MDA，并增强 SOD 活性，而 sST2 则大大减弱了这一作用。
CHF 患者血清中 IL-33 水平升高，特别是全长形式，而 IL-33 生物活性降低。在晚期 CHF 中，IL-33 可能发挥抗氧化作用，但同时升高的 sST2 可能会超过这一作用。
