Beta2-adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12 production in monocytes.
We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on monocyte-derived cytokines, interleukin (IL)-18 and IL-12 production in lipopolysaccharide (LPS)-stimulated monocytes derived from human peripheral blood mononuclear cells (PBMCs), as in vitro model of sepsis. The study found that beta2-AR agonists inhibited IL-18 and IL-12 production in monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar inhibitory pattern of IL-18 and IL-12 production. IL-12 production induced by LPS was inhibited by anti-IL-18 Ab, but IL-18 production by LPS was not inhibited by anti-IL-12 Ab, showing that LPS induced IL-18 production without IL-12 production. Therefore, the stimulation of beta2-AR might be beneficial in the treatment of sepsis through inhibiting LPS-elicited IL-18.
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Kenji
K
Mizuno
Hideo Kohka
HK
Takahashi
Hiromi
H
Iwagaki
Goutaro
G
Katsuno
Huda A S M
HA
Kamurul
Satoru
S
Ohtani
Shuji
S
Mori
Tadashi
T
Yoshino
Masahiro
M
Nishibori
Noriaki
N
Tanaka
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000906:Antibodies / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000906:Antibodies; D020382:Interleukin-18; D008070:Lipopolysaccharides; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12