Influence of lipopolysaccharide exposure on airway function and allergic responses in developing mice.
Exposure to endotoxin has been associated with an exacerbation of asthmatic responses in humans and animal models. However, recent evidence suggests that microbial exposure in early life may protect from the development of asthma and atopy. In this study, we sought to evaluate the effects of lipopolysaccaride (LPS) on airway function in developing mice. In addition, we evaluated the influence of LPS on subsequent allergen sensitization and challenge. Under light anesthesia, 2-3-week-old Balb/c mice received a single intranasal instillation of LPS or sterile physiologic saline. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine (Mch). In additional studies, we assessed the functional and cellular responses to ovalbumin sensitization and challenge following prior exposure to LPS. We found that exposure to LPS induced transient airway hyperresponsiveness to Mch. These functional changes were associated with the recruitment of neutrophils and lymphocytes into the bronchoalveolar lavage (BAL) fluid. Airway responsiveness after allergen sensitization and challenge was decreased by prior exposure to LPS. The analysis of BAL cells and cytokines (interferon-gamma and interleukin-4) did not reveal alterations in the overall Th1/Th2 balance. Our findings suggest that LPS leads to airway hyperresponsiveness in developing mice, and may protect against the development of allergen-driven airway dysfunction.
Department of Pediatrics, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
John R
JR
Cochran
Amir M
AM
Khan
Okan
O
Elidemir
Hasen
H
Xue
Beatrize
B
Cua
Jason
J
Fullmer
Gary L
GL
Larsen
Giuseppe N
GN
Colasurdo
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002452:Cell Count; D016207:Cytokines / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D012016:Reference Values
D016085:Bronchoconstrictor Agents; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D016210:Methacholine Chloride; D010047:Ovalbumin