Participation of β-Adrenergic Receptors on Macrophages in Modulation of LPS-Induced Cytokine Release

Publisher Website
Google Scholar
Abstract
For several years it is known that β-adrenergic receptor agonists have anti-inflammatory effects. However, little is known about the role of β-adrenergic receptors on macrophages in the modulation of cytokine production by β-agonists during inflammation. In this study, the presence of β-receptors on PMA-differentiated U937 human macrophages, and the participation of these receptors in the modulation of LPS-mediated cytokine production by β-agonists was investigated. Total β-receptor expression on undifferentiated (monocyte) and PMA-differentiated U937 cells was established using receptor binding studies on membrane fractions with a radio ligand. The expression of β-receptors proved to be significantly lower on monocytes than on macrophages, additionally a predominant expression of β2-receptors was found. Production of the cytokines TNF-α, IL-6, and IL-10 by LPS-stimulated differentiated U937 cells was measured in time. Peak concentrations for TNF-α, IL-6 and IL-10 occurred at 3, 12 and 9 hrs, respectively. When differentiated U937 cells were incubated with both LPS and the β-agonist clenbuterol the production of TNF-α and IL-6 was significantly reduced. However the production of IL-10 was increased. To study the mechanism of modulation of cytokine production in more detail, U937 macrophages were incubated with LPS/clenbuterol in combination with selective β1- and β2- antagonists. These results indicated that the β2- and not the β1- receptor is involved in the anti-inflammatory activity of clenbuterol.