IN-VIVO EXPRESSION OF CYTOKINE RECEPTOR MESSENGER-RNA IN ATOPIC-DERMATITIS

Background: Atopic dermatitis (AD) is a chronic inflammatory skin dise ase with immunopathologic features that vary depending on the duration of the lesion. Acute lesions are associated with a T-cell infiltrate and a high expression of IL-4 mRNA compared with chronic lesions, unin volved AD skin, or skin from normal control subjects. Chronic lesions are rich in eosinophils and monocyte/macrophages and contain a greater number of IL-5, granulocyte-macrophage colony-stimulating factor (GM- CSF), and IL-12 (p40) mRNA-positive cells. Objectives: In this study, we investigated the mRNA expression of the IL-4 receptor (IL-4R alpha) , IL-5R alpha, GM-CSFR alpha, and IL-12R beta(2) in biopsy specimens f rom acute and chronic AD lesions, uninvolved AD skin, normal skin, and psoriatic skin lesions. Methods: Cytokine receptor mRNA was examined in paraformaldehyde-fixed biopsy specimens with in situ hybridization with specific antisense riboprobes. Results: Acute and chronic skin le sions exhibited a significant increase in numbers of IL-5R alpha and G M-CSFR alpha mRNA-positive cells compared with uninvolved AD skin and normal skin (P <.001). Chronic skin lesions had a significantly greate r number of IL-5R alpha and GM-CSFR alpha mRNA-positive cells when com pared with acute AD skin (P <.001), In contrast, IL-4R alpha mRNA expr ession was increased in acute but not chronic AD lesions compared with uninvolved and normal skin (P <.001). No significant differences were observed in numbers of IL-12R beta(2) mRNA-positive cells when compar ing acute AD, chronic AD, uninvolved AD, and normal skin. In psoriatic skin, the numbers of GM-CSFR alpha and IL-12R beta(2) mRNA-positive c ells were significantly increased compared with acute AD lesions, unin volved skin, and normal control skin (P <.01). Conclusions: These resu lts demonstrate that acute AD is associated with a high expression of IL-4R alpha, whereas IL-5R alpha and GM-CSFR alpha mRNA are predominan tly increased in chronic AD and to lesser extent in acute lesions. The se findings support the biphasic role of IL-4, IL-5, and GM-CSF in the pathophysiology of AD.