title: Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response.
abstract: Regular salbutamol use can exacerbate allergen-induced airway eosinophilia in asthmatics, but its effect on airway eosinophil chemokine responses is unknown. Asthmatic subjects (n=14) were treated for 10 days with placebo or salbutamol in a double-blind, cross-over study, then given same-dose allergen challenges. Their sputa were then analysed 1 and 7 h later for a panel of eosinophil-related cytokines. Eosinophils from five test and three control subjects were tested for expression of CXCL8/interleukin (IL)-8, and its receptors and responsiveness to CCL11/eotaxin and CXCL8/IL-8. Sputum CXCL8/IL-8, but not IL-5, CCL5/regulated on activation, T-cell expressed and secreted, CCL7/monocyte chemotactic protein-3, CCL11/eotaxin, granulocyte-macrophage colony-stimulating factor or tumour necrosis factor levels, were increased (42%) by the salbutamol treatments. The CXCL8/IL-8 levels correlated with the proportions of sputum eosinophils and these cells, but not other sputum cells, stained strongly for CXCL8/IL-8. The circulating eosinophils of the tested subjects (n=5) expressed CXCL8/IL-8 receptors and secreted high levels of this chemokine. Neutralisation of sputum CXCL8/IL-8 reduced eosinophil chemotactic responses to these samples by 19 +/- 5%. These data suggest that regular use of salbutamol can augment airway CXCL8/interleukin-8 responses to allergen challenge and that this CXCL8/interleukin-8 could contribute to the airway inflammatory response.
authors.affiliation: Dept of Veterinary Microbiology, Immunology Research Group, University of Saskatchewan, Division of Respiratory Medicine, Royal University Hospital, Saskatoon, SK, Canada. john.gordon@usask.ca
authors.forename: J R
authors.initials: JR
authors.lastname: Gordon
authors.forename: V A
authors.initials: VA
authors.lastname: Swystun
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: B E
authors.initials: BE
authors.lastname: Davis
authors.forename: P
authors.initials: P
authors.lastname: Hull
authors.forename: D W
authors.initials: DW
authors.lastname: Cockcroft
mesh_terms: D000328:Adult; D000420:Albuterol / Q000008:administration & dosage*; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019743:Chemokines, CXC / Q000276:immunology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000276:immunology; D018709:Statistics, Nonparametric; D015854:Up-Regulation
chemical_list: D001993:Bronchodilator Agents; D019743:Chemokines, CXC; D018836:Inflammation Mediators; D016209:Interleukin-8; D000420:Albuterol