The evaluation of the plasma levels of interleukin 17A, thymic stromal lymphopoietin, interferon gamma, tumor necrosis factor-alpha and interleukins IL-2, IL-6, IL-23, and IL-31 in atopic dermatitis patients with dupilumab treatment

Abstract

Background: Interleukin -17 (IL-17), particularly IL-17A, thymic stromal lymphopoietin (TSLP), interferon gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), IL-2, IL-6, IL-23, and IL-31 play a significant role in the pathogenesis of various chronic inflammatory and autoimmune skin diseases.

Method: We conducted an assessment of plasma levels of interleukins IL-17A, TSLP, IFN-γ TNF-α, IL-2, IL-6, IL-23, and IL-31 in 89 atopic dermatitis (AD) patients and in 34 healthy individuals as a control group. The group of AD patients consisted of 27 patients treated with dupilumab for moderate and severe form (15 men, 12 women, mean age of 44.8 years) and 62 AD patients suffering from moderate and severe form without any systemic treatment (35 women,27 men, mean age of 46.3 years). The control group consisted of 34 healthy subjects (22 men, 12 women, mean age of 43.3 years). For screening analysis of plasma levels of cytokines the performance assay Human cytokine Luminex was used. Blood samples were unstimulated and stimulated with phorbol myristate acetate and ionomycin. The levels of IL-17A, TSLP, IFN-γ, TNF-α, IL-2, IL-6, IL-23, and IL-31 were compared in AD patients with the results in control group. Nonparametric Kruskal-Wallis analysis of variance with post-hoc Dunn's test with Bonferroni modification of significance level was used for statistical analysis.

Results: Under unstimulated conditions we found these significant differences:1) Higher IL-17A and TNF-α in dupilumab-treated AD patients vs. healthy controls, suggesting residual Th17 and pro-inflammatory activity despite Th2 blockade. 2) TSLP elevated in both groups of AD patients indicating persistent epithelial barrier stress. 3) Low IFN-γ in both groups of AD patients is consistent with Th2 dominance. Under stimulated conditions we found these significant differences: 1) Lower IL-23 in both groups of AD patients vs. healthy controls suggesting possible impaired Th17 axis activation. 2) Lower IL-2 in patients without systemic treatment vs. healthy controls indicating reduced T-cell activation capacity without biologic therapy. 3) Higher IL-6 in both groups of AD patients vs. healthy controls reflecting ongoing innate/inflammatory activation under both conditions.

Conclusion: Dupilumab effectively suppresses Th2 signaling but does not fully normalize immune balance; residual Th17 and innate activity persists. Elevated TSLP and IL-6 suggest that epithelial stress and innate immune activation remain key drivers. Reduced IL-23 and IL-2 under stimulation indicate altered adaptive immune responsiveness in AD patients.

Keywords: TSLP; atopic dermatitis; cytokines; dupilumab; inflammation and autoimmunity.