Beta-adrenoceptor stimulation and neutrophil accumulation in mouse airways.
This study characterised the effect of beta-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 involed as mediators. The beta2-adrenoceptor agonist salbutamol (0.025-250 fMol) was administered intranasally in mice 24 h prior to administration of endotoxin (10 microg) 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 beta-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, beta-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.
Miyamoto
M
M
Lung Pharmacology Group, Dept of Respiratory Medicine and Allergology, Institute of Internal Medicine, University of Göteborg, Gothenburg, Sweden.
Tomaki
M
M
Lötvall
J
J
Lindén
A
A
D000281:Administration, Intranasal; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D054426:Chemokine CXCL2; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004347:Drug Interactions; D004731:Endotoxins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D015846:Monokines / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011336:Probability; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012680:Sensitivity and Specificity
D054426:Chemokine CXCL2; D016207:Cytokines; D004731:Endotoxins; D015846:Monokines; D011943:Receptors, Adrenergic, beta; D000420:Albuterol