Atopic asthmatic patients have reduced airway inflammatory cell recruitment after inhaled endotoxin challenge compared with healthy volunteers

作者：Hernandez Michelle L^*; Herbst Margaret; Lay John C; Alexis Neil E; Brickey Willie June; Ting Jenny P Y; Zhou Haibo; Peden David B

来源：Journal of Allergy and Clinical Immunology, 2012, 130(4): 869-+.

DOI：10.1016/j.jaci.2012.05.026

• Asthma
• LPS
• induced sputum
• inflammasome
• innate immunity

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-alpha were significantly increased in both cohorts, but levels of IL-1 beta 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. (J Allergy Clin Immunol 2012; 130:869-76.)

• 出版日期2012-10