Medication with antihistamines impairs allergen-specific immunotherapy in mice.
BACKGROUND
Histamine released from activated mast cells and basophils is an important mediator in allergy. Therefore, antihistamines are efficiently and widely used to suppress allergic symptoms.


OBJECTIVE
This study evaluated the role of antihistamines in sensitization against allergens and in the efficiency of allergen-specific immunotherapy.


METHODS
CBA mice were sensitized and de-sensitized with bee venom allergen extracts and the major allergen phospholipase A2. Clemastine was used to test the effect of a histamine-1 receptor antagonist on the immune responses to phospholipase A2.


RESULTS
The results demonstrated that sensitization against bee venom was strongly enhanced during treatment with antihistamines. Clemastine increased IgE production while decreasing IgG2a production against bee venom. This T-helper type 2 shift of the humoral response appeared to be caused by reduced IFN-gamma and enhanced IL-4 secretion from allergen-specific T cells. We also found reduced TNF-alpha, IL-6 and major histocompatibility complex class-II expression by macrophages. In sensitized mice, the efficiency of allergen-specific immunotherapy was reduced by clemastine treatment.


CONCLUSIONS
Antihistamines may enhance allergic sensitization and reduce the efficiency of allergen-specific immunotherapy. Future studies will need to demonstrate to what extent pre-medication with antihistamine also affects allergen-specific immunotherapy in humans.
Johansen
P
P
Unit for Experimental Immunotherapy, Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. pal.johansen@usz.ch
Senti
G
G
Maria Martínez Gómez
J
J
Kündig
T M
TM
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001514:Bee Venoms / Q000276:immunology*; D002974:Clemastine / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D003888:Desensitization, Immunologic; D015536:Down-Regulation; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006967:Hypersensitivity / Q000503:physiopathology* / Q000628:therapy*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D054467:Phospholipases A2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation
D000485:Allergens; D001514:Bee Venoms; D016207:Cytokines; D006634:Histamine H1 Antagonists; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D002974:Clemastine; D054467:Phospholipases A2