Interleukin-12-independent down-modulation of cockroach antigen-induced asthma in mice by intranasal exposure to bacterial lipopolysaccharide

被引:32
作者
Lundy, SK [1 ]
Berlin, AA [1 ]
Lukacs, NW [1 ]
机构
[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
关键词
D O I
10.1016/S0002-9440(10)63554-7
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Several studies have shown that exposure to bacterial lipopolysaccharide (LPS) can either prevent or inhibit asthma in humans and laboratory rodents. Much emphasis has been placed on the role of cytokines and chemokines in the establishment and maintenance of allergic airway disease. Therefore, it is of interest to study the role of LPS in affecting airway pathology and lung cytokine and chemokine responses in the maintenance phase of asthma. Increasing doses of LPS were administered into the airways of mice presensitized with cockroach allergen (CRAg), then allergic airway disease parameters were assessed after CRAg challenge. Airway hyperresponsiveness after antigen challenge decreased at the highest dose of LPS tested, which was accompanied by a decrease in airway and lung eosinophils. However, a dramatic increase in lung inflammation because of neutrophil influx was observed. Measurement of cytokines in lungs of LPS-treated, CRAg-sensitized mice indicated that interleukin (IL)-12 levels were increased by LPS treatment in a dose-dependent manner, as were levels of several inflammatory chemokines. in contrast, levels of IL-4, IL-13, IL-5, and 11,10 were reduced in whole lung homogenates only of high-dose LPS-treated mice. Intranasal administration of neutralizing anti-IL-12 at the time of high-dose LPS challenge reduced lung IL-12, interferon-gamma, CXCL9, and CXCL10 but did not affect levels of the other chemokines or Th2-type cytokines, and did not restore AHR. These findings suggest that the amelioration of airway hyperresponsiveness observed in LPS-treated, CRAg-sensitized mice is coincident with an immune deviation of the lung inflammatory response, independent of IL-12.
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页码:1961 / 1968
页数:8
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