Effect of Dexamethasone on the Cutaneous Late Phase Response

Abstract

The cutaneous late phase response (LPR) demonstrates characteristics of the inflammatory response associated with acute onset or exacerbations of atopic dermatitis (AD). The current study describes the characterization of the cutaneous LPR in monkeys. Ascaris suum (Asc) sensitive, male cynomolgus monkeys (6-10 kg, n = 4-6) were anesthetized and intradermal injections (40 μL) of PBS or Asc were administered over the thorax/abdominal area. The early phase response (EPR), wheal and flare, was measured 15 minutes post Asc. The LPR was evaluated by analyzing the cellular infiltrate from punch biopsies obtained 20 h after allergen exposure. During treatment studies, monkeys were administered dexamethasone (1 mg/kg; i.m.) 1 h prior to allergen. Asc exposure resulted in a wheal and flare that was significantly (p ≤ 0.04) larger than the paired PBS response. At 20 h post Asc injection a moderate inflammatory response in the upper and deep dermis (p = 0.03) was observed. The LPR was characterized by dermal eosinophilia, and an increase in CD4+ and CD25+ cells, indicative of infiltration and activation of T cells. Pretreatment with dexamethasone had no effect on the Asc-induced EPR, but inhibited the LPR. Dexamethasone significantly inhibited upper dermal inflammation associated with the LPR (p = 0.05) and eosinophilia in both the upper (p = 0.001) and deep (p = 0.05) dermis. With Asc intradermal injection, both an EPR and LPR cutaneous response is observed in the cynomolgus monkey. Acute administration of dexamethasone significantly inhibited the cutaneous LPR. These data elucidate the potential utility of this model for the evaluation of novel therapeutics for AD.