IL-18 in atopic dermatitis-a multifaceted driver of skin inflammation.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by pruritus, barrier dysfunction, and immune cell infiltration. Despite significant progress in our understanding of AD pathophysiology, the molecular mechanisms driving the disease remain only partially elucidated. Recently, the cytokine IL-18, a member of the IL-1 family, has drawn attention for its involvement in diverse immune responses and potential impact on disease severity. In this review, we examine the role of IL-18 in AD, with a focus on genetic associations, biomarker potential, and cellular sources. Elevated IL-18 levels in both the skin and serum of patients with AD are positively correlated with disease severity, type 2 immune response, and impaired barrier function. Mouse models of AD reinforce the importance of IL-18, wherein neutralization or genetic knockout alleviates AD-like features. We further explore how IL-18 drives type 2 immune responses in the skin and the cellular mechanisms involved. Collectively, the present literature supports a crucial role for IL-18 in AD pathophysiology, indicating that targeting IL-18 may be a promising therapeutic strategy for managing the disease.