RT Journal Article
SR Electronic
T1 β‐Adrenoceptor stimulation and neutrophil accumulation in mouse airways
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 231
OP 237
DO 10.1183/09031936.04.00035204
VO 24
IS 2
A1 M. Miyamoto
A1 M. Tomaki
A1 J. Lötvall
A1 A. Lindén
YR 2004
UL http://erj.ersjournals.com/content/24/2/231.abstract
AB This study characterised the effect of β‐adrenoceptor stimulation on endotoxin-induced accumulation of neutrophilic granulocytes in mouse airways, where the cytokines interleukin (IL)‐6 and macrophage inflammatory protein (MIP)‐2 are involved as mediators. The β2‐adrenoceptor agonist salbutamol (0.025–250 fMol) was administered intranasally in mice 24 h prior to administration of endotoxin (10 µg) intranasally. Bronchoalveolar lavage (BAL) fluid and venous blood, respectively, was harvested (6 or 24 h) after administration of endotoxin. Salbutamol substantially decreased the number of neutrophils in BAL fluid from endotoxin-exposed (6 and 24 h) mice and this effect was dose dependent (24 h). Pretreatment with the β‐adrenoceptor antagonist propranolol attenuated the inhibitory effect of salbutamol on BAL neutrophils (6 and 24 h), an attenuation that was not due to any unspecific effect of propranolol. Salbutamol also substantially decreased IL‐6, but not MIP‐2 in BAL fluid (6 h). In contrast to BAL fluid, salbutamol caused a moderate increase in blood neutrophils (24 h). In conclusion, as indicated in mouse airways in vivo, β‐adrenoceptor stimulation prior to endotoxin exposure inhibits the induced accumulation of neutrophils at a time point much later than that anticipated from its bronchodilatory effect. Even though the detailed molecular mechanisms behind this sustained “anti-inflammatory” effect remain unknown, it seems likely that this effect is in part due to a decrease in the local concentration of interleukin‐6. This study was financially supported by the Swedish Heart-Lung Fund, the Swedish Research Council (K2000-71X-090408-11A), the Vårdal Foundation in Sweden and GlaxoSmithKline, UK. No support, direct or indirect, was obtained from the tobacco industry.