Antiinflammatory effects of salmeterol after inhalation of lipopolysaccharide by healthy volunteers.
BACKGROUND
Salmeterol is a beta2-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 microg salmeterol or placebo (t=-0.5 h) followed by 100 microg 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.


RESULTS
Inhalation of LPS was associated with neutrophil influx, neutrophil degranulation (myeloperoxidase, bactericidal/permeability-increasing protein and elastase), release of cytokines (tumor necrosis factor alpha and interleukin 6) and chemokines (interleukin 8, epithelial cell-derived neutrophil attractant 78, macrophage inflammatory proteins 1alpha and 1beta), 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.


CONCLUSIONS
Salmeterol exerts antiinflammatory effects in the pulmonary compartment of humans exposed to LPS.
Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. n.a.maris@amc.uva.nl
Nico A
NA
Maris
Alex F
AF
de Vos
Mark C
MC
Dessing
C Arnold
CA
Spek
Rene
R
Lutter
Henk M
HM
Jansen
Jaring S
JS
van der Zee
Paul
P
Bresser
Tom
T
van der Poll
D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015824:Blood-Air Barrier / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D000068299:Salmeterol Xinafoate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000068299:Salmeterol Xinafoate; D000420:Albuterol