β2-Adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12 production in monocytes

We examined the effects of β2-adrenergic receptor (β2-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 β2-AR agonists inhibited IL-18 and IL-12 production in monocytes, and that AR agonist activity was antagonized by the selective β2-AR antagonist, butoxamine. The selective β2-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 β2-AR might be beneficial in the treatment of sepsis through inhibiting LPS-elicited IL-18.