Allergen dose dependency of the early- and late-phase cutaneous response in the cynomolgus monkey

Authors


Correspondence:
Adrian Tomkinson, Aerovance Inc., 2929 7th Street, Suite 120, Berkeley, CA 94710, USA.
E-mail: adrian.tomkinson@aerovance.com

Summary

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).

Conclusion 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.

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