Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment.
The kinetics of airway inflammation and remodeling processes following ovalbumin aerosol challenge in sensitized BALB/c mice was studied. Mice were exposed to either single or five ovalbumin challenges over 5 days. In both protocols, time-dependent increases in bronchoalveolar lavage (BAL) cellular fibronectin, neutrophils and eosinophils were observed. The kinetics of these events were similar in both protocols; however, the magnitude of the response was much greater following repeated challenges. BAL protein levels and lymphocyte numbers were increased only following repeated challenges, whereas interleukin (IL)-5 and IL-4 were increased in both protocols. Histological analysis revealed a time-dependent increase in epithelial cell proliferation and in mucus-producing epithelial cells. Proliferation of alveolar cells was observed only following repeated challenges. Airway hyperreactivity was observed in both protocols but was much greater following repeated challenges. Pretreatment with dexamethasone fully inhibited the inflammatory response and airway hyperreactivity but only partially inhibited the remodeling process. These data suggest that glucocorticoids, although potent anti-inflammatory agents, may not be potent in reducing the lung remodeling process associated with asthma.
Trifilieff
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A
Novartis Horsham Research Center, Horsham RH12 5AB, United Kingdom.
El-Hashim
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A
Bertrand
C
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016085:Bronchoconstrictor Agents; D002455:Cell Division / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D015848:Interleukin-5 / Q000032:analysis / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010949:Plasma / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D005353:Fibronectins; D015848:Interleukin-5; D016210:Methacholine Chloride; D015847:Interleukin-4; D007073:Immunoglobulin E; D003907:Dexamethasone; D010047:Ovalbumin