Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: an antiallergic activity.
BACKGROUND
It is well known that allergen-specific nasal challenge (ASNC) is a fruitful tool with which to evaluate antiallergic activity exerted by a drug. Azelastine is a new antihistamine also available in topical form (i.e., nasal spray).


OBJECTIVE
The aim of the study was to evaluate the effects of azelastine nasal spray on inflammatory changes after ASNC in both the early-phase reaction and the late-phase reaction.


METHODS
The study had a double-blind, placebo-controlled, randomized, and parallel-group design. Twenty patients with pollen allergy were enrolled out of pollen season. ASNC was performed at baseline (TO) and after 1 week of washout (T7). At T7, 10 patients sprayed azelastine (1 puff) into their nostrils, and 10 patients used placebo. ASNC was performed after 30 minutes. The considered parameters (evaluated during early- and late-phase reactions) were: (1) clinical signs and symptoms, (2) cytologic assessment (neutrophils and eosinophils), (3) assay-of mediators (eosinophil cationic protein and myeloperoxidase), and (4) expression of intercellular adhesion molecule-1 (ICAM-1) on nasal epithelial cells. We focused our attention on ICAM-1 because it is the natural ligand of leukocyte functional associated antigen-1 and Mac-1, expressed on eosinophils. In addition, ICAM-1 is expressed on epithelial cells only on allergen exposure (both natural and experimental).


RESULTS
Placebo did not exert any modification on the considered parameters. After azelastine administration, significant decreases in total symptom score, eosinophilic and neutrophilic infiltration, and ICAM-1 expression were observed during both early- and late-phase reactions. Furthermore, serum eosinophil cationic protein levels decreased during the late-phase reaction, whereas myeloperoxidase was not affected by the treatment. These findings were confirmed by the powerful Koch's split-plot statistical analysis.


CONCLUSIONS
Azelastine exerts antiallergic activity, mainly affecting eosinophil function and downregulating ICAM-1 expression, on nasal epithelial cells.
Ciprandi
G
G
Department of Internal Medicine, Genoa University, Italy.
Pronzato
C
C
Passalacqua
G
G
Ricca
V
V
Grögen
J
J
Mela
G S
GS
Varese
P
P
Bertolini
C
C
Bagnasco
M
M
Canonica
G W
GW
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000187:drug effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001798:Blood Proteins / Q000096:biosynthesis; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009299:Nasal Provocation Tests; D009195:Peroxidase / Q000096:biosynthesis; D010793:Phthalazines / Q000008:administration & dosage / Q000494:pharmacology*; D012260:Ribonucleases
D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D006634:Histamine H1 Antagonists; D018836:Inflammation Mediators; D010793:Phthalazines; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D012260:Ribonucleases; C020976:azelastine