Abstract | RATIONALE: OBJECTIVE: 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. MEASUREMENTS AND MAIN 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. CONCLUSION:
Salmeterol exerts antiinflammatory effects in the pulmonary compartment of humans exposed to LPS.
|
Authors | Nico A Maris, Alex F de Vos, Mark C Dessing, C Arnold Spek, Rene Lutter, Henk M Jansen, Jaring S van der Zee, Paul Bresser, Tom van der Poll |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 172
Issue 7
Pg. 878-84
(Oct 01 2005)
ISSN: 1073-449X [Print] United States |
PMID | 15994467
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Adrenergic beta-Agonists
- Lipopolysaccharides
- RNA, Messenger
- Tumor Necrosis Factor-alpha
- Salmeterol Xinafoate
- Albuterol
|
Topics |
- Adrenergic beta-Agonists
(pharmacology, therapeutic use)
- Adult
- Albuterol
(analogs & derivatives, pharmacology, therapeutic use)
- Blood-Air Barrier
(drug effects)
- Bronchoalveolar Lavage Fluid
(cytology)
- Flow Cytometry
- Humans
- Lipopolysaccharides
- Lung
(drug effects, physiology)
- Macrophages, Alveolar
(metabolism)
- Male
- Neutrophil Infiltration
(drug effects)
- RNA, Messenger
(metabolism)
- Salmeterol Xinafoate
- Tumor Necrosis Factor-alpha
(metabolism)
- Up-Regulation
(drug effects)
|