Carvedilol, a nonselective β-blocker, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro

摘要: Tumor necrosis factor (TNF) and tissue (TF) produced by monocytes macrophages have been shown to be among the aggravating factors for chronic heart failure (CHF), because they induce cardiac dysfunction thrombotic complications, respectively. Carvedilol, a nonselective β-adrenoceptor antagonist with α 1 - adrenoceptor blockade action, has demonstrated improve outcome of patients severe CHF, suggesting that carvedilol might inhibit production TNF TF. In this study, possibility is examined using isolated human stimulated lipopolysaccharide (LPS) in vitro . Carvedilol (10 μM) significantly inhibited LPS-induced TF monocytes, whereas prazosin (a selective -adrenoceptor antagonist), bisoprolol β ICI-118,551 2 arotinolol action) did not. both expression early growth response factor-1 (Egr-1) phosphorylation extracellular signal-regulated kinase (ERK) 1/2, but it not activation either nuclear factor-κB or activator protein-1 LPS. These results suggest inhibits inhibiting ERK1/2–Egr-1 pathway independent its inhibitory activities monocytes.