The beta-adrenoceptor agonist clenbuterol is a potent inhibitor of the LPS-induced production of TNF-alpha and IL-6 in vitro and in vivo

Objective and Design: To investigate the suppressive effects of the beta-ag onist clenbuterol on the release of TNF-alpha and IL-6 in a lipopolysacchar ide (LPS)-model of inflammation, both in vitro and in vivo. Material and Subjects: Human U-937 cell line (monocyte-derived macrophages) , and male Wistar rats (200-250 g). Treatment: U-937 macrophages were incubated with LPS at 1 mu g/ml, with or without 1.0 mM-0.1 nM test drugs (clen-buterol and other cAMP elevating age nts) for 1-24 h. Rats were administered either 1 or 10 mu g/kg clenbuterol (or saline) orally, 1 h before intraperitoneal administration of 2 mg/kg LP S. Methods and Results: TNF-alpha and IL-6 time-concentration profiles were de termined both in culture media and plasma, using ELISA's and bioassays. LPS -mediated release of both cytokines was significantly suppressed by clenbut erol. Conclusions: The beta-agonist clenbuterol very potently suppresses the LPS- induced release of the pro-inflammatory cytokines TNF-alpha and IL-6 both i n vitro and in vivo.