In vivo expression of cytokine receptor mRNA in atopic dermatitis

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease 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, uninvolved 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-4Rα), IL-5Rα, GM-CSFRα, and IL-12Rβ 2 in biopsy specimens from 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 lesions exhibited a significant increase in numbers of IL-5Rα and GM-CSFRα mRNA-positive cells compared with uninvolved AD skin and normal skin ( P < .001). Chronic skin lesions had a significantly greater number of IL-5Rα and GM-CSFRα mRNA-positive cells when compared with acute AD skin ( P < .001). In contrast, IL-4Rα mRNA expression 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-12Rβ 2 mRNA-positive cells when comparing acute AD, chronic AD, uninvolved AD, and normal skin. In psoriatic skin, the numbers of GM-CSFRα and IL-12Rβ 2 mRNA-positive cells were significantly increased compared with acute AD lesions, uninvolved skin, and normal control skin ( P < .01). Conclusions: These results demonstrate that acute AD is associated with a high expression of IL-4Rα, whereas IL-5Rα and GM-CSFRα mRNA are predominantly increased in chronic AD and to lesser extent in acute lesions. These findings support the biphasic role of IL-4, IL-5, and GM-CSF in the pathophysiology of AD. (J Allergy Clin Immunol 1998;102:245-50)