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


CONCLUSIONS
Addition of multiple time points earlier than 1 month would be valuable to establish the time point of maximum induction in cell apoptosis.


CONCLUSIONS
Etanercept selectively induces apoptosis of pathogenic dermal dendritic cells in responding patients early in the course of treatment.
Malaviya
Rama
R
Division of Clinical Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA. rmalaviya@earthlink.net
Sun
Yvonne
Y
Tan
Jennifer K
JK
Wang
Andrew
A
Magliocco
Melissa
M
Yao
Melissa
M
Krueger
James G
JG
Gottlieb
Alice B
AB
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects*; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology* / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects*; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use*
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept