Desloratadine inhibits allergen-induced airway inflammation and bronchial hyperresponsiveness and alters T-cell responses in murine models of asthma.
BACKGROUND
Histamine elicits many features of immediate hypersensitivity reactions. Recent evidence indicates that H1 receptors modulate immune responses to antigens. Desloratadine (DL), a new, long-acting, H1 receptor antagonist, has both a potent antihistaminic function and anti-inflammatory properties.


OBJECTIVE
We sought to evaluate the effect of DL on allergic-airway responses in mice after inhalation of the naturally occurring aeroallergen Aspergillus fumigatus (Af ) and to examine the effects of DL on specific immune responses to a defined protein antigen with the use of an ovalbumin (OVA) model of asthma.


METHODS
Mice were subjected either to repeated, intranasal application of Af extract or to intraperitoneal immunization with OVA, followed by inhalation challenge. DL or a control fluid was given daily throughout the sensitization process. Immunoglobulin E (IgE) levels, bronchoalveolar lavage-fluid cytokines and cytology, lung histology, and physiologic responses to methacholine were assessed in the allergen-treated mice. Anti-OVA IgE responses and OVA-driven T-cell cytokine production were examined.


RESULTS
Treatment with DL did not impair IgE production but did inhibit bronchial inflammation and bronchial hyperresponsiveness in both Af- and OVA-treated mice. This inhibition required that DL be administered concurrently with allergen sensitization, indicating that the attenuation of bronchial hyperresponsiveness and inflammation was not caused by anticholinergic receptor effects. OVA-responsive T cells from DL-treated mice exhibited depressed production of IL-4, IL-5, and IL-13 and normal amounts of interferon-gamma. The amounts of IL-5 and IL-13 were also diminished in the bronchoalveolar lavage fluid.


CONCLUSIONS
DL, given at the time of exposure to the allergen, inhibits T(H)2 responses, the induction of allergic pulmonary inflammation, and bronchial hyperresponsiveness. These results suggest that DL or similar agents given during times of antigen exposure might alter disease progression in patients with respiratory allergy.
Bryce
Paul J
PJ
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Geha
Raif
R
Oettgen
Hans C
HC
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000517:prevention & control*; D017336:Loratadine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011969:Receptors, Histamine H1 / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D039563:Histamine H1 Antagonists, Non-Sedating; D011969:Receptors, Histamine H1; D007073:Immunoglobulin E; D017336:Loratadine; D010047:Ovalbumin; C121345:desloratadine