Effects of fexofenadine on T-cell function in a murine model of allergen-induced airway inflammation and hyperresponsiveness.
There is renewed interest in antihistamines for the treatment of allergic asthma. A growing body of literature has shown that the newer compounds can affect inflammatory cell accumulation and cytokine/chemokine production. In a murine model of allergen-induced airway inflammation and hyperresponsiveness, the ability of fexofenadine to affect these outcomes was tested in a primary sensitization and challenge model and after treatment of donor mice before the adoptive transfer of T cells into recipients receiving limited allergen exposure. Mice were sensitized and challenged with allergen (ovalbumin). Airway function after inhaled methacholine was monitored in parallel to the assessment of tissue and airway inflammation and cytokine production. In further experiments, lung T lymphocytes from sensitized/challenged donor mice were transferred into naive recipients before limited airway challenge with the allergen. Administration of fexofenadine before challenge but after sensitization was effective in preventing tissue eosinophilia and airway hyperresponsiveness. Moreover, the treatment of donor mice with fexofenadine before transfer of lung T cells effectively prevented airway hyperresponsiveness and eosinophilia in naive mice exposed to limited airway challenge. These data therefore support the potential for fexofenadine in the treatment of allergen-induced airway hyperresponsiveness and inflammation.
Gelfand
Erwin W
EW
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Cui
Zhi-Hua
ZH
Takeda
Katsuyuki
K
Kanehiro
Arihiko
A
Joetham
Anthony
A
D000280:Administration, Inhalation; D019264:Adoptive Transfer; D000485:Allergens / Q000009:adverse effects* / Q000187:drug effects*; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects / Q000276:immunology; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects* / Q000187:drug effects*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000209:etiology*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000209:etiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000485:Allergens; D018926:Anti-Allergic Agents; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D006634:Histamine H1 Antagonists; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D016593:Terfenadine; D010047:Ovalbumin; C093230:fexofenadine