title: Beta 2-adrenergic receptor agonist induces IL-18 production without IL-12 production.
abstract: Endogenous catecholamine, epinephrine and norepinephrine, and isoproterenol concentration-dependently induced the production of interleukin (IL)-18, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, and inhibited that of IL-10 in human peripheral blood mononuclear cells (PBMC). All responses by these stimulations were antagonized by the selective beta 2-adrenergic receptor (AR) antagonist, butoxamine, but not by alpha 1-, alpha 2- and beta 1-AR antagonists. The selective beta 2-AR agonists, salbutamol and terbutaline, induced a similar pattern of cytokine production, indicating that the effect of these AR agonists on cytokine production was through beta 2-AR stimulation. Anti-IL-18 Ab or caspase-1 inhibitor prevented all increase/decrease effects, suggesting that IL-18 might affect the production of all other cytokines. While endogenous IL-18 produced by salbutamol and terbutaline reached a sufficient concentration to induce IL-12 production, these beta 2-AR agonists did not induce the production of IL-12 at all. Epinephrine/norepinephrine/isoproterenol/beta 2-AR agonists increased the production of IL-18 in monocytes, but had no effect on IL-12, TNF-alpha, IFN-gamma and IL-10 production. The lack of beta 2-AR-induced effect on IL-12 production was due to a beta 2-AR-induced inhibition of an IL-18-elicited upregulation of both CD40 and CD40 ligand (CD40L/CD154) expressions on monocytes. The sympathetic innervating lymphoid organs may be under the control of beta2-AR stimulation, maintaining the basal cytokine environment in the tissues.
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Hideo K
authors.initials: HK
authors.lastname: Takahashi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwagaki
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D001782:Blood Donors; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D018674:Adrenergic Antagonists; D000318:Adrenergic beta-Agonists; D019013:CD40 Antigens; D016207:Cytokines; D020382:Interleukin-18; D018343:Receptors, Adrenergic, beta-2; D023201:CD40 Ligand; D018664:Interleukin-12