Fexofenadine modulates T-cell function, preventing allergen-induced airway inflammation and hyperresponsiveness.

Abstract

BACKGROUND:

Antihistamines have been evaluated for usefulness in the treatment of asthma for more than 50 years. Interest was limited until the introduction of newer compounds that were free of much of the dose-limiting sedation associated with the earlier drugs.

OBJECTIVE:

In a murine model of allergen-induced airway inflammation and hyperresponsiveness, the efficacy of an H1 receptor antagonist to prevent allergic inflammation and altered airway function was evaluated.

METHODS:

Mice were sensitized and challenged to an allergen, ovalbumin, which elicited marked airway and tissue eosino-philia and airway hyperresponsiveness. Fexofenadine was administered before challenge, and airway responsiveness to inhaled methacholine, airway and tissue eosinophilia, bronchoalveolar lavage fluid cytokine levels, and serum IgE levels were assayed. In a second group of experiments, sensitized and challenged mice were treated or not treated with fexofenadine before challenge. T cells were isolated from the lungs and adoptively transferred into naive recipients before exposure to limited airway allergen challenge, and lung function and inflammation were evaluated.

RESULTS:

Fexofenadine treatment of sensitized mice prevented the development of airway hyperresponsiveness in both the primary sensitization and challenge, as well as in the adoptive transfer experiments. These changes were accompanied by decreases in bronchoalveolar lavage and tissue eosinophilia, lymphocyte numbers, and T(H)2 cytokine production.

CONCLUSION:

The results demonstrate the efficacy of an H1 receptor antagonist in preventing allergen-induced alterations in pulmonary inflammation and airway function. The data support the evaluation of drugs such as fexofenadine in the treatment of allergic asthma.

• Authors: Erwin W Gelfand, Zhi-Hua Cui, Katsuyuki Takeda, Arihiko Kanehiro, Anthony Joetham
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 110 Issue 1 Pg. 85-95 (Jul 2002) ISSN: 0091-6749 [Print] United States
• PMID: 12110826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Allergens
• Anti-Allergic Agents
• Cytokines
• Terfenadine
• fexofenadine

Topics

• Adoptive Transfer
• Allergens (immunology)
• Animals
• Anti-Allergic Agents (pharmacology, therapeutic use)
• Bronchial Hyperreactivity (drug therapy, immunology, physiopathology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• Cytokines (biosynthesis)
• Disease Models, Animal
• Female
• Inflammation (drug therapy, immunology, physiopathology)
• Lung (cytology)
• Mice
• Mice, Inbred BALB C
• T-Lymphocytes (drug effects, immunology, metabolism)
• Terfenadine (analogs & derivatives, pharmacology, therapeutic use)