Effect of β2-Adrenergic Receptor Stimulation on Interleukin-18-Induced Intercellular Adhesion Molecule-1 Expression and Cytokine Production

• Published in: The Journal of pharmacology and experimental therapeutics 2003-02, Vol.304 (2), p.634-642
• Main Authors: Takahashi, Hideo Kohka, Morichika, Toshihiko, Iwagaki, Hiromi, Yoshino, Tadashi, Tamura, Ryuji, Saito, Shinnya, Mori, Shuji, Akagi, Tadaatsu, Tanaka, Noriaki, Nishibori, Masahiro
• Format: Article
• Language: English
• ISSN: 0022-3565
• DOI: 10.1124/jpet.102.042622

β-Adrenergic receptor (AR) agonists have been demonstrated to modulate the production of inflammatory mediators. Recent studies implied that β2-AR agonists might be useful for chronic inflammatory diseases caused by interleukin (IL)-18. In the present study, we found that norepinephrine, epinephrine, or isoproterenol down-regulated IL-18 (100 ng/ml)-induced intercellular adhesion molecule (ICAM)-1 expression on monocytes in a dose-dependent manner (10−8–10−4 M), but did not effect B7.1 and B7.2 expression after 24-h incubation. The modulatory effect of these catecholamines on ICAM-1 expression was antagonized by β2-AR antagonist, but not by α1-, α2-, or β1-AR antagonist. β2-AR-selective agonists salbutanol and terbutaline down-regulated IL-18-induced ICAM-1 expression on monocytes, but α1-, α2-, or β1-AR agonist had no effect. In the same manner, salbutanol and terbutaline as well as norepinephrine, epinephrine, and isoproterenol regulated the IL-18-induced cytokine production, including IL-12, tumor necrosis factor-α or interferon-γ through the stimulation of β2-AR. Together with the previous finding that ICAM-1/lymphocyte function-associated antigen-1 interaction plays a crucial role in the IL-18-initiated cytokine network, the present study strongly suggested that the stimulation of β2-AR inhibited the IL-18-activated cytokine cascade through the inhibitory effect on ICAM-1 expression, contributing to finding a new method for clinical treatment.