2006 Volume 45 Issue 7 Pages 429-434
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.
