Antiinflammatory effects of salmeterol after inhalation of lipopolysaccharide by healthy volunteers

Rationale: Salmeterol is a beta(2)-adrenoreceptor agonist used in the treatment of obstructive pulmonary disease. Salmeterol inhibits inflammatory responses by neutrophils and mononuclear cells in vitro and in mouse models of lung inflammation in vivo. Objective: To determine the effect of salmeterol on LPS-induced lung inflammation in humans. Methods: Thirty-two healthy subjects were enrolled in a single-blinded, placebo-controlled study. Subjects inhaled 100 mu g salmeterol or placebo (t = -0.5 h) followed by 100 mu g LPS or normal saline (t = 0 h; n = 8/group). Measurements were performed in bronchoalveolar lavage fluid and purified alveolar macrophages obtained 6 h post-challenge. Measurements and Main Results: Inhalation of LIPS was associated with neutrophil influx, neutrophil degranulation (myeloperoxidase, bactericidal/permeability-increasing protein and elastase), release of cytokines (tumor necrosis factor a and interleukin 6) and chemokines (interleukin 8, epithelial cell-derived neutrophil attractant 78, macrophage inflammatory proteins 1 alpha and 1 P), activation of alveolar macrophages (upregulation of HLA-DR and CD71; enhanced expression of mRNAs for 13 different mediators of inflammation), and protein leakage (all p < 0.05 vs. placebo/saline). Pretreatment with salmeterol inhibited LPS-induced neutrophil influx, neutrophil degranulation (myeloperoxidase), tumor necrosis factor alpha release, and HLA-DR expression (all p < 0.05 vs. placebo/LPS), while not significantly influencing other responses. Conclusion: Salmeterol exerts antlinflammatory effects in the pulmonary compartment of humans exposed to LPS.