Oral administration of desloratadine prior to sensitization prevents allergen-induced airway inflammation and hyper-reactivity in mice.
BACKGROUND
Histamine-1-receptor (H1R)-antagonists were shown to influence various immunological functions on different cell types and may thus be employed for immune-modulating strategies for the prevention of primary immune responses.


OBJECTIVE
The aim of this study was to investigate the effects of an H1R-antagonist on allergen-induced sensitization, airway inflammation (AI) and airway hyper-reactivity (AHR) in a murine model.


METHODS
BALB/c mice were systemically sensitized with ovalbumin (OVA) (six times, days 1-14) and challenged with aerosolized allergen (days 28-30). One day prior to the first and 2 h prior to every following sensitization, mice received either 1 or 0.01 microg of desloratadine (DL) or placebo per os.


RESULTS
Sensitization with OVA significantly increased specific and total IgE and IgG1 serum levels, as well as in vitro IL-5 and IL-4 production by spleen and peribronchial lymph node (PBLN) cells. Sensitized and challenged mice showed a marked eosinophilic infiltration in broncho-alveolar lavage fluids and lung tissues, and developed in vivo AHR to inhaled methacholine. Oral treatment with DL prior to OVA sensitization significantly decreased production of OVA-specific IgG1, as well as in vitro Th2-cytokine production by spleen and PBLN cells, compared with OVA-sensitized mice. Moreover, eosinophilic inflammation and development of in vivo AHR were significantly reduced in DL-treated mice, compared with sensitized controls.


CONCLUSIONS
Treatment with H1R-anatagonist prior to and during sensitization suppressed allergen-induced Th2 responses, as well as development of eosinophilic AI and AHR. This underscores an important immune modulating function of histamine, and implies a potential role of H1R-anatagonists in preventive strategies against allergic diseases.
Blümchen
K
K
Department of Pediatric Pneumology and Immunology, University Hospital Charite, Berlin, Germany.
Gerhold
K
K
Thorade
I
I
Seib
C
C
Wahn
U
U
Hamelmann
E
E
D000284:Administration, Oral; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D016535:Bronchial Hyperreactivity; D002478:Cells, Cultured; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D017336:Loratadine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin; D013154:Spleen / Q000276:immunology
D000485:Allergens; D006634:Histamine H1 Antagonists; D007074:Immunoglobulin G; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D017336:Loratadine; D010047:Ovalbumin; C121345:desloratadine