Central Neurotranspeptide, Alpha-Melanocyte-Stimulating Hormone (α-MSH) is Upregulated in Patients with Congestive Heart Failure
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概要
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Background: α-melanocyte-stimulating hormone (α-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. Objective: To determine if α-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. Methods: The circulating levels of α-MSH were measured in 115 patients with CHF using a double-antibody radioimmunoassay. To determine one of the sources of circulating α-MSH, human peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α. Furthermore, to clarify one of the functions of α-MSH, PBMC were cultured in the presence or absence of α-MSH. Results: Plasma levels of α-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 α-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-α released α-MSH in a concentration-dependent manner. α-MSH inhibited LPS-induced TNF-α production, and α-MSH simultaneously augmented production of interleukin (IL)-10 by PBMC. Conclusions: Circulating α-MSH was increased in patients with CHF. Inflammatory response induced α-MSH production in cultured human PBMC. Treatment of α-MSH could modify the immunobalance between inflammatory and anti-inflammatory responses in cultured PBMC. These findings suggest that α-MSH may play an important role in the pathophysiology of CHF.
著者
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Shioi Tetsuo
Department Of Cardiology And Internal Medicine Kitasato University School Of Medicine
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Yamaoka-tojo Minako
Department of Cardiology, Kitasato University School of Medicine
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Inomata Takayuki
Department Of Cardio-angiology Kitasato University School Of Medicine
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Yamaoka-tojo Minako
Department Of Cardioangiology Kitasato University School Of Medicine
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Masuda Takashi
Departmant Of Emergency & Critical Care Medicine Kitasato University School Of Medicine
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Izumi Tohru
Department Of Angio-cardiology Kitasato University School Of Medicine
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Tojo Taiki
Department Of Angio-cardiology Kitasato University School Of Medicine
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Izumi Tohru
Department of Cardiology, Kitasato University School of Medicine
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Inomata Takayuki
Department of Cardiology, Kitasato University School of Medicine
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Tojo Taiki
Department of Cardiology, Kitasato University School of Medicine
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