Inhibitory effects of the beta-adrenergic receptor agonist zilpaterol on the LPS-induced production of TNF-alpha 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.

• Authors: K C M Verhoeckx, R P Doornbos, J van der Greef, R F Witkamp, R J T Rodenburg
• Journal: Journal of veterinary pharmacology and therapeutics (J Vet Pharmacol Ther) Vol. 28 Issue 6 Pg. 531-7 (Dec 2005) ISSN: 0140-7783 [Print] England
• PMID: 16343285 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Agonists
• Immunologic Factors
• Lipopolysaccharides
• Trimethylsilyl Compounds
• Tumor Necrosis Factor-alpha
• Zilpaterol
• Cyclic AMP

Topics

• Adrenergic beta-Agonists (administration & dosage, pharmacology)
• Animals
• Cattle
• Cyclic AMP (metabolism)
• Dose-Response Relationship, Drug
• Escherichia coli
• Humans
• Immunologic Factors (administration & dosage, pharmacology)
• Lipopolysaccharides
• Macrophage Activation (drug effects)
• Male
• Rats
• Rats, Wistar
• Trimethylsilyl Compounds (administration & dosage, pharmacology)
• Tumor Necrosis Factor-alpha (drug effects, metabolism)
• U937 Cells (drug effects, metabolism)