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.