title: Transient corticosteroid treatment permanently amplifies the Th2 response in a murine model of asthma.
abstract: Corticosteroids (CS) remain the most efficacious pharmacotherapeutic option for the management of asthma. Although the acute anti-inflammatory effects of CS treatment have been amply documented both clinically and experimentally, recent human data intimate that exposure to CS may be associated with retrograde immune phenomena, including enhanced synthesis of IgE in vivo and elevated Th2 cytokine production in vitro. We have investigated the long-term immunologic effects of CS treatment in a murine model of allergic airway inflammation. CS treatment during initial exposure to OVA or upon long-term Ag rechallenge remarkably attenuated eosinophilic airway inflammation and airway hyperresponsiveness. Interestingly, however, Th2 cytokine production by cultured splenocytes from CS-treated mice was significantly elevated, while IFN-gamma synthesis was depressed. Moreover, mice rechallenged with OVA several weeks after CS intervention during allergic sensitization not only developed airway inflammation, but also exhibited enhanced Th2 cytokine production in lymphoid tissues and OVA-specific IgE in serum. This amplification of the systemic immune response was associated with an intact APC compartment during CS-conditioned sensitization to OVA. These data indicate that immune processes underlying the allergic phenotype remain impervious to CS treatment and raise the possibility that treatment with CS during sensitization may amplify elements of the allergen-specific immune response.
authors.affiliation: Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. wileyr@mcmaster.ca
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Wiley
authors.forename: Monika
authors.initials: M
authors.lastname: Cwiartka
authors.forename: David
authors.initials: D
authors.lastname: Alvarez
authors.forename: David C
authors.initials: DC
authors.lastname: Mackenzie
authors.forename: Jill R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Susanna
authors.initials: S
authors.lastname: Goncharova
authors.forename: Lennart
authors.initials: L
authors.lastname: Lundblad
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007156:Immunologic Memory / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009330:Nebulizers and Vaporizers; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D019819:Budesonide; D010047:Ovalbumin