RATIONALE: 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. 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.
RCT Entities:
RATIONALE: 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. 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: Raminder Aul; Jane Armstrong; Annelyse Duvoix; David Lomas; Brian Hayes; Bruce E Miller; Chris Jagger; Dave Singh Journal: Br J Clin Pharmacol Date: 2012-12 Impact factor: 4.335
Authors: Markus Bosmann; Jamison J Grailer; Ketong Zhu; Michael A Matthay; J Vidya Sarma; Firas S Zetoune; Peter A Ward Journal: FASEB J Date: 2012-02-07 Impact factor: 5.191
Authors: M Elizabeth Wilcox; M Patricia Rivera; Catherine Sassoon; Lorraine B Ware; Hannah Wunsch; Margaret S Herridge Journal: Proc Am Thorac Soc Date: 2012-10
Authors: Jelger J van der Meer; Onno J de Boer; Peter Teeling; Chris M van der Loos; Mark C Dessing; Allard C van der Wal Journal: Int J Clin Exp Pathol Date: 2011-03-22
Authors: Anil Sapru; Ludmila Pawlikowska; Kathleen D Liu; Kiran K Khush; Lee Ann-Baxter-Lowe; Vanessa Hayden; Rebecca L Menza; Maureen Convery; Annie Poon; Megan Landeck; Jonathan G Zaroff; Michael A Matthay Journal: J Heart Lung Transplant Date: 2011-02 Impact factor: 10.247
Authors: Murali Shyamsundar; Scott T W McKeown; Cecilia M O'Kane; Thelma R Craig; Vanessa Brown; David R Thickett; Michael A Matthay; Clifford C Taggart; Janne T Backman; J Stuart Elborn; Daniel F McAuley Journal: Am J Respir Crit Care Med Date: 2009-03-26 Impact factor: 21.405