Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis

Dupilumab is a monoclonal antibody approved for the treatment
of
atopic dermatitis (AD); however, its effects on molecular, cellular,
and immunological levels remain to be elucidated. In this study, blood
and dermal interstitial fluid (ISF) from nonlesional (NL) and lesional
(L) skin were collected from eight patients with moderate to severe
AD, before (visit 2-v2) and at the end of a 16-week treatment with
dupilumab (visit 10-v10). Clinical treatment effect was demonstrated
by significantly decreased AD severity scores at the end of treatment.
At v10 versus v2, the percentages of CD4+ interleukin-producing cells
showed a decreasing trend in ISF L and NL, unbound IL-4 levels in
plasma were increased, IL-5 levels in ISF L reduced, and levels of
factors involved in anti-inflammatory pathways and re-epithelization
increased. At v2, ISF L showed that AD lesions might have altered
amino acid pathways and lipid signaling compared to ISF NL. At v10,
ISF L exhibited raised levels of long- and very-long-chain fatty acids
and lipids compared to v2. Furthermore, dupilumab administration caused
reduced expression of miR-155–5p and miR-378a-3p in ISF L.
In conclusion, results from the present study provided novel knowledge
by linking local immune and metabolic alterations to AD pathogenesis
and treatment response.