Background
Atopic dermatitis (AD) is the most common inflammatory disease. Evolving disease models link changes in epidermal growth and differentiation to Th2/Th22 cytokine activation. However, these models have not been tested by in-vivo suppression of T-cell cytokines. CsA is an immune-suppressant highly effective for severe disease, but its mechanism in AD skin lesions has not been studied.
Objective
To establish the ability of a systemic immune-suppressant to modulate immune and epidermal alterations that form the pathogenic disease phenotype, and to correlate changes with clinical improvement.
Methods
CsA effects on AD skin pathology were evaluated using geneexpression and immunohistochemistry studies in baseline, week 2 and 12 lesional and non-lesional biopsies from 19 patients treated with 5 mg/kg/d CsA for 12 weeks.
Results
After 2 and 12 weeks of treatment, we observed significant reductions of 51% and 72%, respectively, in Scoring of AD/SCORAD. Clinical improvements were associated with significant gene expression changes in lesional but also non-lesional skin, particularly reductions of Th2-, Th22-, and some Th17-related molecules (i.e IL-13, IL-22, CCL17, S100As, elafin/PI3), and modulation of epidermal hyperplasia and differentiation measures.
Conclusions
This is the first study that establishes a relationship between cytokine activation and molecular epidermal alterations as well as correlations between disease biomarkers in the skin and clinical improvement. The reversal of the molecular phenotype with CsA and the associated biomarkers can serve as a reference for the successful modulation of tissue inflammation with specific immune-antagonists in future studies, contributing to the understanding of the specific cytokines involved in epidermal pathology.