title: Lipopolysaccharide exposure makes allergic airway inflammation and hyper-responsiveness less responsive to dexamethasone and inhibition of iNOS.
abstract: Allergic airway disease can be refractory to anti-inflammatory treatment, whose cause is unclarified. Therefore, in the present experiment, we have tested the hypothesis that co-exposure to lipopolysacharide (Lps) and allergen results in glucocorticoid-resistant eosinophil airway inflammation and hyper-responsiveness (AHR). Ovalbumin (Ova)-sensitized BALB/c mice were primed with 10 microg intranasal Lps 24 h before the start of Ova challenges (20 min on 3 consecutive days). Dexamethasone (5 mg/kg/day) was given on the last 2 days of Ova challenges. AHR, cellular build-up, cytokine and nitrite concentrations of bronchoalveolar lavage fluid (BALF) and lung histology were examined. To assess the role of iNOS-derived NO in airway responsiveness, mice were treated with a selective inhibitor of this enzyme (1400W) 2 h before AHR measurements. More severe eosinophil inflammation and higher nitrite formation were found in Lps-primed than in non-primed allergized mice. After Lps priming, AHR and concentrations of T-helper type 2 cytokines in BALF were decreased, but still remained significantly higher than in controls. Eosinophil inflammation was partially, while nitrite production and AHR were observed to be largely dexamethasone resistant in Lps-primed allergized animals. 1400W effectively and rapidly diminished the AHR in Ova-sensitized and challenged mice, but failed to affect it after Lps priming plus allergization. In conclusion, Lps inhalation may exaggerate eosinophil inflammation and reduce responsiveness to anti-inflammatory treatment in allergic airway disease.
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Z I
authors.initials: ZI
authors.lastname: Komlósi
authors.forename: E
authors.initials: E
authors.lastname: Pozsonyi
authors.forename: T
authors.initials: T
authors.lastname: Tábi
authors.forename: E
authors.initials: E
authors.lastname: Szöko
authors.forename: A
authors.initials: A
authors.lastname: Nagy
authors.forename: B
authors.initials: B
authors.lastname: Bartos
authors.forename: G T
authors.initials: GT
authors.lastname: Kozma
authors.forename: L
authors.initials: L
authors.lastname: Tamási
authors.forename: M
authors.initials: M
authors.lastname: Orosz
authors.forename: P
authors.initials: P
authors.lastname: Magyar
authors.forename: G
authors.initials: G
authors.lastname: Losonczy
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D007097:Imines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D007097:Imines; D008070:Lipopolysaccharides; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D009566:Nitrates; D009573:Nitrites; D003907:Dexamethasone; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II