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
To investigate the suppressive effects of the beta-agonist clenbuterol on the release of TNF-alpha and IL-6 in a lipopolysaccharide (LPS)-model of inflammation, both in vitro and in vivo.


METHODS
Human U-937 cell line (monocyte-derived macrophages), and male Wistar rats (200-250 g).


METHODS
U-937 macrophages were incubated with LPS at 1 microg/ml, with or without 1.0 mM-0.1 nM test drugs (clenbuterol and other cAMP elevating agents) for 1-24 h. Rats were administered either 1 or 10 microg/kg clenbuterol (or saline) orally, 1 h before intraperitoneal administration of 2 mg/kg LPS.


RESULTS
TNF-alpha and IL-6 time-concentration profiles were determined both in culture media and plasma, using ELISA' s and bioassays. LPS-mediated release of both cytokines was significantly suppressed by clenbuterol.


CONCLUSIONS
The beta-agonist clenbuterol very potently suppresses the LPS-induced release of the pro-inflammatory cytokines TNF-alpha and IL-6 both in vitro and in vivo.
Izeboud
C A
CA
Department of Pharmacology, TNO Pharma, Zeist, The Netherlands. Izeboud@voeding.tno.nl
Monshouwer
M
M
van Miert
A S
AS
Witkamp
R F
RF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002976:Clenbuterol / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002976:Clenbuterol