Resiquimod, a new immune response modifier from the family of imidazoquinolinamines, inhibits allergen-induced Th2 responses, airway inflammation and airway hyper-reactivity in mice.
BACKGROUND
Allergen-induced sensitization and airway disease are the results of adverse immune reactions against environmental antigens that may be prevented or inhibited by immune modifying strategies.


OBJECTIVE
To investigate the effects of the novel immune response modifier resiquimod (R-848), from the family of imidazol-derivates, in a murine model of allergen-mediated Th2-immune responses and concomitant airway inflammation and airway hyper-reactivity.


METHODS
BALB/c mice were systemically sensitized with ovalbumin (OVA) on days 1 and 14 and challenged with OVA aerosol on days 28 and 29. R-848 was applied intranasally to sensitized animals once prior to the first allergen airway challenge, on day 27.


RESULTS
A single application of R-848 significantly reduced numbers of eosinophils and lymphocytes in bronchoalveolar lavage fluid and inhibited mucus gland hyperplasia, compared with sensitized and challenged controls. Associated with the decrease in airway inflammation, single intranasal treatment with R-848 abolished the development of airway hyper-reactivity after allergen sensitization and airway challenges. Additionally, Th2-cytokine production in lung tissues from sensitized and R-848-treated animals was reduced, whereas IL-12 and IFN-gamma production was increased, compared with non-treated sensitized mice.


CONCLUSIONS
These data indicate that R-848 effectively inhibits allergen-induced airway inflammation and hyper-reactivity by modulation of increased Th2-immune responses.
Quarcoo
D
D
Department of Pediatric Pneumology and Immunology, Charité-Humboldt University, Berlin, Germany.
Weixler
S
S
Joachim
R A
RA
Stock
P
P
Kallinich
T
T
Ahrens
B
B
Hamelmann
E
E
D000485:Allergens / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001980:Bronchi / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D007093:Imidazoles; D007155:Immunologic Factors; D015848:Interleukin-5; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; C402365:resiquimod