title: Treatment with cyclosporin A during sensitization with trimellitic anhydride attenuates the airway responses to allergen challenge three weeks later.
abstract: The present studies examined the effects of oral treatment with cyclosporin A, betamethasone or azelastine administered over the time of sensitization with trimellitic anhydride on allergen-induced airway responses, compared to those of control animals given corn oil alone. Drugs were given for 8 days. The animals were sensitized with trimellitic anhydride (0.1 ml of 0.3% w/v) in corn oil given intradermally on days 4 and 5 of drug treatment. Three to four weeks after sensitization with free trimellitic anhydride, the animals were anesthetized, tracheostomized and challenged with trimellitic anhydride conjugated to guinea pig serum albumin (trimellitic anhydride-guinea pig serum albumin; 0.5%; 50 microliters) instilled via the airway route. In the same animal, we measured both lung resistance (RL) to monitor airflow obstruction, and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. In control animals, instillation of trimellitic anhydride-guinea pig serum albumin into the tracheal lumen caused a slowly progressing increase in RL over the observation period (6 min), in addition to extravasation of Evans Blue dye at all airway levels. In animals treated with 50 mg/kg of cyclosporin A, both the allergen-induced increase in RL and extravasation of Evans Blue dye in intrapulmonary airways were significantly attenuated. However, neither betamethasone nor azelastine significantly affected these responses. We conclude that cyclosporin A may influence the immune system in the guinea pig during the induction of allergy, thus leading to attenuation of allergen-induced airway obstruction at later time points.
authors.affiliation: Department of Clinical Pharmacology, University of Göteborg, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Arakawa
authors.forename: P
authors.initials: P
authors.lastname: Andius
authors.forename: I
authors.initials: I
authors.lastname: Kawikova
authors.forename: B E
authors.initials: BE
authors.lastname: Skoogh
authors.forename: C G
authors.initials: CG
authors.lastname: Löfdahl
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D000284:Administration, Oral; D000403:Airway Resistance / Q000187:drug effects*; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006967:Hypersensitivity / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D010793:Phthalazines / Q000008:administration & dosage / Q000494:pharmacology; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000276:immunology*; D012709:Serum Albumin; D013047:Specific Pathogen-Free Organisms
chemical_list: D000485:Allergens; D006634:Histamine H1 Antagonists; D007074:Immunoglobulin G; D010793:Phthalazines; D010796:Phthalic Anhydrides; D012709:Serum Albumin; C015559:trimellitic anhydride; D016572:Cyclosporine; D001623:Betamethasone; C020976:azelastine