Etanercept induces apoptosis of dermal dendritic cells in psoriatic plaques of responding patients.

ABSTRACT

BACKGROUND: Etanercept is a tumor necrosis factor-alpha binding fusion protein that demonstrates efficacy in the treatment of psoriasis, which is accompanied by decreased plaque infiltration of T cells and myeloid dendritic cells. We hypothesized that etanercept decreases inflammatory cell infiltration by inducing apoptosis. OBJECTIVE: We sought to investigate the effect of etanercept on circulating and plaque leukocyte apoptosis in psoriasis. METHODS: Blood and plaque specimens were obtained from 10 patients with psoriasis treated with etanercept (25 mg subcutaneously twice weekly) for 24 weeks. Apoptosis was determined in tissue samples using immunohistochemistry and flow cytometry. RESULTS: Etanercept selectively induced apoptosis in dermal dendritic cells in plaques of responding patients at 1 month, before most of the clinical and histologic response was achieved. No apoptosis was detected in plaque or circulating T cells or in circulating monocytes. LIMITATIONS: Addition of multiple time points earlier than 1 month would be valuable to establish the time point of maximum induction in cell apoptosis. CONCLUSION: Etanercept selectively induces apoptosis of pathogenic dermal dendritic cells in responding patients early in the course of treatment.