Participation of beta-adrenergic receptors on macrophages in modulation of LPS-induced cytokine release

J Recept Signal Transduct Res. Jan-Jul 1999;19(1-4):191-202. doi: 10.3109/10799899909036645.

Abstract

For several years it is known that beta-adrenergic receptor agonists have anti-inflammatory effects. However, little is known about the role of beta-adrenergic receptors on macrophages in the modulation of cytokine production by beta-agonists during inflammation. In this study, the presence of beta-receptors on PMA-differentiated U937 human macrophages, and the participation of these receptors in the modulation of LPS-mediated cytokine production by beta-agonists was investigated. Total beta-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 beta-receptors proved to be significantly lower on monocytes than on macrophages, additionally a predominant expression of beta 2-receptors was found. Production of the cytokines TNF-alpha, IL-6, and IL-10 by LPS-stimulated differentiated U937 cells was measured in time. Peak concentrations for TNF-alpha, IL-6 and IL-10 occurred at 3, 12 and 9 hrs, respectively. When differentiated U937 cells were incubated with both LPS and the beta-agonist clenbuterol the production of TNF-alpha 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 beta 1- and beta 2-antagonists. These results indicated that the beta 2- and not the beta 1-receptor is involved in the anti-inflammatory activity of clenbuterol.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Atenolol / pharmacology
  • Clenbuterol / pharmacology
  • Cytokines / biosynthesis
  • Cytokines / metabolism*
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Propanolamines / pharmacology
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • U937 Cells

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Cytokines
  • Interleukin-6
  • Lipopolysaccharides
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • ICI 118551
  • Atenolol
  • Clenbuterol