Allergen dose dependency of the early- and late-phase cutaneous response in the cynomolgus monkey.
BACKGROUND
Cutaneous administration of allergen provides a means to confirm an allergic status, investigate the pathogenesis of allergic diseases, and/or provide a mechanism to evaluate the benefit of new potential therapeutics.


OBJECTIVE
Studies were performed to characterize the allergen-induced cutaneous early- and late-phase response (EPR and LPR) in the cynomolgus monkey.


METHODS
Following intradermal injections of Ascaris suum allergen, the cutaneous weal and flare EPR was measured 15 min post-injection, and skin biopsies were collected at 8-24 h to determine the optimal time of LPR occurrence. Biopsies were analysed for epidermal and dermal inflammatory changes.


RESULTS
The EPR was dose related with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100 allergen dilution. In contrast, the threshold dose required for a reproducible LPR was much greater requiring a dilution of 6 : 100, suggesting independent mechanisms for the EPR and LPR. The LPR 20 h post-allergen injection induced an inflammatory response in the upper and deep dermis. The response was characterized by a moderate perivascular to diffuse inflammation consisting of mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis, P<0.001; deep dermis, P=0.02).


CONCLUSIONS
Collectively, the results indicate the dose dependency of the EPR and LPR. Furthermore, our observations indicate the value of the LPR response in the cynomolgus monkey to evaluate new therapeutics for the treatment of allergic diseases such as atopic dermatitis.
Tomkinson
A
A
Department of Preclinical Development, Aerovance Inc., Berkeley, CA 94710, USA. adrian.tomkinson@aerovance.com
Morton
M
M
Stevens
L
L
Bowden
A
A
Tepper
J
J
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D000835:Animals, Wild; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004306:Dose-Response Relationship, Immunologic; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000276:immunology*; D007150:Immunohistochemistry; D008252:Macaca fascicularis / Q000276:immunology*; D008297:Male; D012867:Skin / Q000276:immunology* / Q000473:pathology; D012882:Skin Tests
D000485:Allergens; D003907:Dexamethasone