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Relationship of the Specific Inflammatory Cytokines KLK5, IL-8, and IL-22 with Demodex Density and Risk Factors in Rosacea

Jingang Xu,Yao Zhang,Chao Ci,Xiaohong Lu,Xin Hu,Jinhong Zhao,Yuanyuan Li

Published 2025 in Journal of Inflammation Research

ABSTRACT

Objective This study aimed to analyze the differences in serum KLK5, IL-8, and IL-22 levels between patients with rosacea and healthy controls, compare the severity of Demodex mite infection between the two groups, explore the risk factors for the occurrence of rosacea, and to further explore the relationship between the severity of Demodex mite infection, risk factors and the levels of inflammatory cytokines. Methods A total of 27 rosacea patients and 10 volunteers without any skin diseases were enrolled to assess Demodex mite infestation using reflectance confocal microscopy (RCM) and to evaluate rosacea severity by clinician erythema assessment (CEA) and investigator global assessment (IGA). Serum inflammatory cytokines were measured by ELISA. Additionally, lifestyle factors were surveyed via questionnaire in 30 rosacea patients and 30 volunteers. Results Elevated levels of KLK5, IL-8, and IL-22 were observed in the rosacea group compared with healthy controls (P < 0.05). Dermoscopy revealed a higher density of Demodex mites in rosacea patients. Questionnaire analysis identified nine factors (age, gender, rest frequency, anxiety, sleep quality, smoking, drinking, allergy history, and family history) significantly associated with rosacea risk. After multivariate adjustment, age and poor sleep quality remained independent risk factors. Furthermore, severe Demodex infection correlated with significantly higher KLK5 and IL-8 levels than mild infection (P < 0.05). Among patients, anxiety was linked to increased KLK5 and IL-22, while poor sleep quality was associated with elevated KLK5 and IL-8. Conclusion We demonstrated a strong association between Demodex mite density and rosacea development. Importantly, significant elevations in serum KLK5, IL-8, and IL-22 were identified, supporting the role of Demodex mites in activating specific inflammatory pathways. The study further identified age and sleep quality as independent risk factors, underscoring the influence of psychological and lifestyle factors.

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