Abstract: 【Abstract】 Objective To investigate the correlation between serum vitamin D levels and macrophage inflammation in children with atopic dermatitis （AD） of different severity. Methods Data were retrospectively collected from 122 children diagnosed with AD at the Department of Dermatology, Children′s Hospital of Soochow University between August 2022 and May 2024. According to the diagnosis and disease severity, the patients were classified into mild, moderate, and severe AD groups, and 30 healthy children undergoing medical checkups during the same period were selected as a control group. A generalized linear mixed-effects model was used to analyze the association between serum vitamin D levels and the risk of pediatric AD. The dose-response relationship between serum vitamin D levels and the severity of severe AD was analyzed by the restricted cubic spline method. Hierarchical interaction analysis was conducted to assess the association between serum vitamin D levels and severe pediatric AD under different conditions, and multiple linear regression analysis was performed to examine the correlations between vitamin D levels and inflammation-related indicators. Results A total of 122 children with AD were included, comprising 65 males and 57 females, aged 6.23 ± 1.34 years （range, 2 - 9 years）, with a disease duration of 4.47 ± 0.84 months. Among them, 54 had mild AD, 36 had moderate AD, and 32 had severe AD. The control group included 30 healthy children （16 males and 14 females） aged 6.16 ± 1.27 years. No significant differences were observed among the 4 groups in age or gender distribution （both P > 0.05）. Significant differences were found among the 4 groups in skin dryness severity, pruritus intensity, eczematous lesion area, serum IgE levels, eosinophil counts, serum vitamin D levels, and levels of interleukin （IL）-4, IL-6, tumor necrosis factor-α （TNF-α）, and interferon-γ （IFN-γ） （all P < 0.05）. Compared with the other 3 groups, the severe AD group showed higher eosinophil counts and elevated serum levels of IgE, IL-4, IL-6, TNF-α, and IFN-γ, but lower serum vitamin D levels （all P < 0.05）. Generalized linear mixed-effects model analysis showed a negative correlation between serum vitamin D levels and the risk of pediatric AD. Restricted cubic spline analysis showed that serum vitamin D levels were negatively correlated with the severity of severe pediatric AD （P < 0.05）. In particular, when serum vitamin D levels exceeded 37.54 ng/ml, the risk of severe pediatric AD decreased significantly with increasing vitamin D levels （P < 0.05）. Hierarchical interaction analysis demonstrated negative associations between serum vitamin D levels and the severity of severe pediatric AD across subgroups with different levels of IgE, IL-4, IL-6, and TNF-α （all P < 0.05）. Multiple linear regression analysis showed that serum vitamin D levels were correlated with the levels of inflammatory markers IL-4, IL-6, and TNF-α, all of which exerted significant mediating effects on the association between serum vitamin D levels and pediatric AD severity （P < 0.001）. Conclusions Serum vitamin D levels were negatively correlated with the severity of severe pediatric AD. Furthermore, IL-4, IL-6, and TNF-α could mediate the association between vitamin D levels and pediatric AD severity.

Key words: Dermatitis, atopic, Child, Vitamin D, Macrophage inflammation, Mediating effects, Interleukin