Atherosclerosis is an inflammatory disease in the vessel wall. IL-6 is a mediator of inflammation and a major alarm hormone signaling tissue damage and infection to the body's host defense system, in particular to the liver, where it induces the synthesis of acute phase plasma proteins. Although Norepinephrine (NE) can stimulate the vascular cells to produce IL-6, it is unknown whether NE induces IL-6 expression in macrophages. The present study was to observe effect of NE on IL-6 production and the related signal pathway in U937 macrophages so as to provide more evidence for the proinflammatory action of NE. The results showed that NE significantly increased mRNA and protein expression of IL-6 in U937 macrophages in time- and concentration-dependent manners. beta-adrenoreceptor inhibitor propranolol blocked NE-induced IL-6 expression in mRNA and protein levels in U937 macrophages. Propranolol and DPI [NAD(P)H oxidase inhibitor] decreased NE-stimulated reactive oxygen species (ROS) generation, and antioxidant NAC completely abolished NE-induced IL-6 expression in U937 macrophages. The further study indicated that NAD(P)H oxidase inhibitor DPI and NF-kappa B inhibitor PDTC reduced NE-induced mRNA and protein expression of IL-6 in U937 macrophages. These demonstrate that NE is capable of inducing IL-6 generation in macrophages via beta-ADR-ROS-NF-kappa B signal pathway, which contributes to better understanding of the proinflammatory and proatherosclerotic actions of NE. (C) 2015 Elsevier Inc. All rights reserved.