Related Experiment Videos
TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques
Alice B Gottlieb1, Francesca Chamian, Salman Masud
1Clinical Research Center, University of Medicine and Dentistry of New Jersey -Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. alice.gottlieb@umdnj.edu
Journal of Immunology (Baltimore, Md. : 1950)
|August 6, 2005
Summary
Etanercept treatment rapidly reduces key inflammatory genes and immune cells in psoriasis plaques. This TNF/lymphotoxin blockade disrupts the cycle of immune cell activation, improving skin inflammation.
Area of Science:
- Immunology
- Dermatology
- Pharmacology
Background:
- Mechanisms of TNF-blocking drugs in lesional tissues remain unclear.
- Psoriasis plaques offer accessibility for repeat biopsies to study drug effects.
Purpose of the Study:
- To investigate the effects of etanercept (TNF/lymphotoxin blockade) on psoriasis plaques.
- To evaluate histological response, gene expression, and cellular infiltration after 6 months of treatment.
Main Methods:
- Ten psoriasis patients underwent repeat biopsies during 6 months of etanercept treatment.
- Histological analysis, inflammatory gene expression profiling, and cellular infiltration assessment were performed.
Main Results:
- Rapid reduction in IL-1 and IL-8 mRNA, followed by other inflammation-related genes.
- Progressive decrease in myeloid cells (CD11c+) and T lymphocytes observed.
- Decreased expression of chemokines (CXCL10, CCL20) correlated with reduced immune cell infiltration.
Conclusions:
- Etanercept disrupts the self-sustaining cycle of immune cell activation in psoriasis.
- Reduced dendritic cell (DC) activation and subsequent T cell activation contribute to therapeutic effects.
- TNF/lymphotoxin blockade with etanercept reverses epidermal hyperplasia and cutaneous inflammation in psoriasis.