Yamaoka-Tojo Minako, Tojo Taiki, Shioi Tetsuo, Masuda Takashi, Inomata Takayuki, Izumi Tohru
Department of Cardiology, Kitasato University School of Medicine, Sagamihara.
Intern Med. 2006;45(7):429-34. doi: 10.2169/internalmedicine.45.1546. Epub 2006 May 1.
Alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin (POMC) derivative, is a neuropeptide with potent anti-inflammatory properties that inhibits tissue injury in a wide array of inflammation models.
To determine if alpha-MSH is involved in the development of congestive heart failure (CHF) with the specific aim of examining its peripheral source and one of the mechanisms.
The circulating levels of alpha-MSH were measured in 115 patients with CHF using a double-antibody radioimmunoassay. To determine one of the sources of circulating alpha-MSH, human peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha. Furthermore, to clarify one of the functions of alpha-MSH, PBMC were cultured in the presence or absence of alpha-MSH.
Plasma levels of alpha-MSH were significantly higher in NYHA class II patients with CHF than in control subjects (p<0.0001). A significant correlation was found between the levels of alpha-MSH and high-sensitive testing for C-reactive protein in patients with CHF (r=0.41, p<0.0005). PBMC stimulated with LPS or TNF-alpha released alpha-MSH in a concentration-dependent manner. alpha-MSH inhibited LPS-induced TNF-alpha production, and alpha-MSH simultaneously augmented production of interleukin (IL)-10 by PBMC.
Circulating alpha-MSH was increased in patients with CHF. Inflammatory response induced alpha-MSH production in cultured human PBMC. Treatment of alpha-MSH could modify the immunobalance between inflammatory and anti-inflammatory responses in cultured PBMC. These findings suggest that alpha-MSH may play an important role in the pathophysiology of CHF.
α-黑素细胞刺激素（α-MSH）是一种促肾上腺皮质激素原（POMC）衍生物，是一种具有强大抗炎特性的神经肽，可在多种炎症模型中抑制组织损伤。
确定α-MSH是否参与充血性心力衰竭（CHF）的发生发展，具体目的是研究其外周来源及其中一种机制。
采用双抗体放射免疫分析法测定115例CHF患者循环中α-MSH的水平。为确定循环中α-MSH的来源之一，用人外周血单核细胞（PBMC）与脂多糖（LPS）或肿瘤坏死因子（TNF）-α进行刺激。此外，为阐明α-MSH的功能之一，在有或无α-MSH的情况下培养PBMC。
纽约心脏协会（NYHA）心功能II级的CHF患者血浆α-MSH水平显著高于对照组（p<0.0001）。CHF患者中α-MSH水平与C反应蛋白高敏检测结果之间存在显著相关性（r=0.41，p<0.0005）。用LPS或TNF-α刺激的PBMC以浓度依赖方式释放α-MSH。α-MSH抑制LPS诱导的TNF-α产生，同时α-MSH增强PBMC产生白细胞介素（IL）-10。
CHF患者循环中α-MSH升高。炎症反应可诱导培养的人PBMC产生α-MSH。α-MSH治疗可改变培养的PBMC中炎症和抗炎反应之间的免疫平衡。这些发现表明α-MSH可能在CHF的病理生理学中起重要作用。
