A32-26 Salmeterol Induces Il-6 in Bronchial Epithelial and Subepithelial Cells In Vivo

Rationale Studies have shown induction of the inflammatory mediator IL-6 by β2 agonists in bronchial epithelial cells (BECs) in vitro. The addition of an inhaled corticosteroid (ICS) to β2 agonists suppressed these effects. We evaluated the response of airway IL-6 to salmeterol monotherapy and salmeterol/fluticasone combination therapy in people with asthma in vivo. Methods 23 participants aged ≥18 years with mild asthma underwent a study involving 1 week of β2 agonist washout (baseline 1) followed by 2 weeks daily treatment with inhaled salmeterol xinafoate 200µg, followed by another 2 week washout period (baseline 2), and finally 2 weeks treatment of inhaled salmeterol xinafoate/fluticasone propionate 200µg/1mg daily. Bronchial biopsies were collected during bronchoscopies at the end of the washout and treatment periods. Bronchial biopsies were fixed and stained with an anti-IL-6 primary antibody, HRP secondary antibody and counterstained with haematoxylin. Immunostaining positivity for IL-6 expression was quantified using the hybrid (H)-score system (1:2). Outcomes were compared using the Wilcoxon test. Results Salmeterol induced IL-6 in BECs (P < 0.0001) compared to baseline 1. Salmeterol also induced IL-6 and inflammatory cell counts in the sub-epithelium (P < 0.0001) compared to baseline 1. Salmeterol/fluticasone combination therapy suppressed subepithelial IL-6 and inflammatory cell counts (P = 0.0003) compared to salmeterol monotherapy. Conclusion Salmeterol induced IL-6 and inflammatory cells in the airways of asthma participants in vivo potentially contributing to increased airway inflammation.