β2-Adrenergic receptor agonist induces IL-18 production without IL-12 production

Hideo K. Takahashi, Hiromi Iwagaki, Shuji Mori, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Endogenous catecholamine, epinephrine and norepinephrine, and isoproterenol concentration-dependently induced the production of interleukin (IL)-18, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and inhibited that of IL-10 in human peripheral blood mononuclear cells (PBMC). All responses by these stimulations were antagonized by the selective β2-adrenergic receptor (AR) antagonist, butoxamine, but not by α1-, α2- and β1-AR antagonists. The selective β2-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 β2-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 β2-AR agonists did not induce the production of IL-12 at all. Epinephrine/norepinephrine/isoproterenol/ β2-AR agonists increased the production of IL-18 in monocytes, but had no effect on IL-12, TNF-α, IFN-γ and IL-10 production. The lack of β2-AR-induced effect on IL-12 production was due to a β2-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 β2-AR stimulation, maintaining the basal cytokine environment in the tissues.

Original languageEnglish
Pages (from-to)137-147
Number of pages11
JournalJournal of Neuroimmunology
Volume151
Issue number1-2
DOIs
Publication statusPublished - Jun 2004

Keywords

  • Adhesion molecules
  • Cytokines
  • Human
  • Monocytes/macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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