title: Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers.
abstract: BACKGROUND
  Atopic asthmatic patients are reported to be more sensitive to the effects of environmental endotoxin (LPS) than healthy volunteers (HVs). It is unknown whether this sensitivity is due to dysregulated inflammatory responses after LPS exposure in atopic asthmatic patients.
  
  
  OBJECTIVE
  We sought to test the hypothesis that atopic asthmatic patients respond differentially to inhaled LPS challenge compared with HVs.
  
  
  METHODS
  Thirteen allergic asthmatic (AA) patients and 18 nonallergic nonasthmatic subjects (healthy volunteers [HVs]) underwent an inhalation challenge to 20,000 endotoxin units of Clinical Center Reference Endotoxin (LPS). Induced sputum and peripheral blood were obtained at baseline and 6 hours after inhaled LPS challenge. Sputum and blood samples were assayed for changes in inflammatory cell numbers and cytokine and cell-surface marker levels on monocytes and macrophages.
  
  
  RESULTS
  The percentage of neutrophils in sputum (%PMN) in induced sputum similarly and significantly increased in both HVs and AA patients after inhaled LPS challenge. However, the absolute numbers of leukocytes and PMNs recruited to the airways were significantly lower in AA patients compared with those seen in HVs with inhaled LPS challenge. Sputum levels of IL-6 and TNF-α were significantly increased in both cohorts, but levels of IL-1β and IL-18 were only significantly increased in the HV group. Cell-surface expression of Toll-like receptors 4 and 2 were significantly enhanced only in the HV group.
  
  
  CONCLUSIONS
  The airway inflammatory response to inhaled LPS challenge is blunted in AA patients compared with that seen in HVs and accompanied by reductions in airway neutrophilia and inflammasome-dependent cytokine production. These factors might contribute to increased susceptibility to airway microbial infection or colonization in AA patients.
authors: Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27516, USA. Michelle_Hernandez@med.unc.edu
authors: Michelle L
authors: ML
authors: Hernandez
authors: Margaret
authors: M
authors: Herbst
authors: John C
authors: JC
authors: Lay
authors: Neil E
authors: NE
authors: Alexis
authors: Willie June
authors: WJ
authors: Brickey
authors: Jenny P Y
authors: JP
authors: Ting
authors: Haibo
authors: H
authors: Zhou
authors: David B
authors: DB
authors: Peden
mesh_terms: D000328:Adult; D001249:Asthma / Q000473:pathology*; D002465:Cell Movement; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D013183:Sputum / Q000166:cytology; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4