The role of cytokines/chemokines in the pathogenesis of atopic dermatitis

Abstract

Atopic dermatitis (AD) is the most common and relapsing allergic disease of the skin. AD is characterized by a predominant expression of Th2-type cytokines associated with increased cellular infiltration in the skin, elevated circulating levels of IgE and eosinophilia. These findings are positively correlated with interleukin (IL)-4 and IL-13 expression in CD4+ T cells. In AD patients, Th2 cells, eosinophils, mast cells and dendritic cells are markedly increased in the skin lesions. However, Th1 cells are also involved in the development of AD lesions. In fact, Th1 cytokine mRNA expressions including γ-interferon and IL-12 are elevated in the chronic lesions as well as elevated Th2 cytokines in the acute AD lesions. The discovery of Th17 lineage and regulatory T (T(reg)) cells shifted the simple Th1/Th2 balance concept into a 4-way balance system. Th17/22 cells, Foxp3+ T(reg) and IL-10-producing T cells (Tr1) are involved in the mechanism of a local and systemic immunological milieu. In addition, super Th1 cells arranged from Th1 cells in high IL-18 milieu are also involved in the development of mouse AD lesions. Correction of Th2 cytokine predominance by Th1 inducers shows effectiveness in experimental models. However, fine-tuning of the delicate 4-way balance among Th1, Th2, Th17/22 and T(reg) cells is required for the control of AD. Efficacy of some biological agents in AD has been reported. However, further investigations are required to make possible the therapeutic application of biologicals, antigen-specific immunotherapy, non-antigen-specific immunotherapy, antagonists and biological response modifiers in the clinic. These novel approaches may constitute a potential curative therapy for AD.