TY - JOUR T1 - Effect of β2-Adrenergic Receptor Stimulation on Interleukin-18-Induced Intercellular Adhesion Molecule-1 Expression and Cytokine Production JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 634 LP - 642 DO - 10.1124/jpet.102.042622 VL - 304 IS - 2 AU - Hideo Kohka Takahashi AU - Toshihiko Morichika AU - Hiromi Iwagaki AU - Tadashi Yoshino AU - Ryuji Tamura AU - Shinnya Saito AU - Shuji Mori AU - Tadaatsu Akagi AU - Noriaki Tanaka AU - Masahiro Nishibori Y1 - 2003/02/01 UR - http://jpet.aspetjournals.org/content/304/2/634.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -