Effects of anti-allergy drugs on th1 cell and th2 cell development mediated by langerhans cells

Abstract

Background: Langerhans cells (LCs) are involved in T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. We examined the effects of various anti-allergy drugs against the Th2 cell development by LCs. Methods: The expression of cell surface molecules on LCs was investigated using RT-PCR. The effects of anti-allergy drugs on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Next, mice were primed via the hind footpad with ovalbumin (OVA)-pulsed LCs that had been treated with selected anti-allergy drugs, cyproheptadine, promethazine, emedastine and loratadine. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The therapeutic effects of a finally selected drug, emedastine on atopic dermatitis (AD) were assessed using in NC/Nga mice. Results: OVA peptide-pulsed LCs that had been treated with each drug and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production. The LCs that had been treated with emedastine also inhibited Th1 cell development, as represented by down-regulation of interferon (IFN)-γ production. This was accompanied by suppression of CD40 expression in LCs. Topical application of emedastine significantly suppressed the increase in the skin severity score in NC/Nga mice. This suppressive effect was associated with a decrease in the production of IFN-γ and IL-4 in auricular lymph node cells. Conclusions: Topical application of emedastine may be beneficial in AD-like skin lesions by inhibiting both Th1 cell and Th2 cell development mediated by LCs.