Inhibitory effects of the β₂‐adrenergic receptor agonist zilpaterol on the LPS‐induced production of TNF‐α in vitro and in vivo

Abstract

In this study the anti-inflammatory properties of zilpaterol, a beta2-adrenergic receptor (AR) agonist specifically developed as a growth promoter in cattle were investigated. Although zilpaterol has a different structure compared with the beta2-AR agonists known to date, it was noted that it was able to bind to both the beta2-AR (Ki = 1.1 x 10(-6)) and the beta1-AR (Ki = 1.0 x 10(-5)). Using lipopolysaccharide (LPS)-exposed U937 macrophages, the production of cyclic adenosine-3',5'-cyclic monophosphate (cAMP) and tumor necrosis factor alpha (TNF-alpha) were investigated. Zilpaterol inhibited TNF-alpha release and induced intracellular cAMP levels in a dose-dependent manner. The inhibition of TNF-alpha release and induction of cAMP production was mainly mediated via the beta2-AR, as indicated by addition of beta1- and beta2-specific antagonists. The effects of zilpaterol were investigated in LPS-treated male Wistar rats after pretreatment with zilpaterol. Zilpaterol dosed at 500 microg/kg body weight reduced the TNF-alpha plasma levels. In conclusion, zilpaterol is a beta2-adrenergic agonist and an inhibitor of TNF-alpha production induced by LPS both in vivo and in vitro.

Salbutamol inhibits lipopolysaccharide-induced inflammatory responses in rat peritoneal macrophages

“…These reports suggest that HO-1 protein and its enzymatic products ameliorate inflammatory disease via anti-inflammatory effects. Izeboud et al (1999) and Verhoeckx et al (2005) have demonstrated that β 2 -AR agonists had the inhibition effects on the LPS-induced production of proinflammatory cytokines both in human U-937 cell line (monocytederived macrophages) and in rats. Liaw et al (2003) have revealed that β 2 -AR agonists suppressed TNF-α and NO production via iNOS in LPS treated rats.…”

Time-dependent effect of in vivo inflammation on eicosanoid and endocannabinoid levels in plasma, liver, ileum and adipose tissue in C57BL/6 mice fed a fish-oil diet

“…saline or 3 mg/kg LPS. In previous studies, we and others have shown that this procedure induces an acute generalized inflammatory response [22]. At t = 0, and after 2, 4, 8, and 24 h respectively, four animals from both the saline and the LPS groups were anesthetized (only four saline treated animals at t = 0), blood was collected from the orbital sinus, captured in 1.3 mL EDTA coated tubes (Sarstedt; Etten-Leur, The Netherlands) and put on ice until centrifugation (10′, 10,000 rpm at 4°C).…”

Screening of mimetic peptides for CD14 binding site with LBP and antiendotoxin activity of mimetic peptide in vivo and in vitro

“…TNF-a is an inflammatory factor produced by most inflammatory cells stimulated by LPS [27,28]. It can induce more inflammatory factors, which play a key role in the occurrence and development of SIRS (Systemic Inflammatory Response Syndrome) [29,30].…”