MAST-CELLS ARE ONE MAJOR SOURCE OF INTERLEUKIN-4 IN ATOPIC-DERMATITIS

Several reports have shown the presence of T-helper lymphocytes with T h2 characteristics in the skin lesions of atopic dermatitis (AD). Howe ver, Th2 cells themselves require an exogenous pulse of IL-4 to initia te their differentiation and synthesis of IL-4. As mast cells have rec ently been shown to contain IL-4, this finding prompted us to investig ate IL-4 in mast cells of AD lesions, to determine if they might provi de the IL-4 pulse needed by the Th2 cells. In this study, we measured IL-4 immunoreactivity in mast cells of non-lesional and lesional skin sections from 20 patients with AD. Ten patients with nummular eczema ( NE) without any atopic features or background, and five healthy subjec ts, served as the control groups. Mast cells were first identified usi ng an enzyme-histochemical staining method for tryptase. Subsequently, the sections were photographed, the tryptase stain was removed, and I L-4 was demonstrated with a polyclonal antibody. The sections were pho tographed again, and the percentage of IL-4-positive mast cells was ca lculated. The percentage of mast cells exhibiting IL-4 immunoreactivit y in the upper dermis in lesional vs. non-lesional skin was 66 +/- 18% vs. 37 +/- 18% in AD (P < 0.0001, paired t-test), but only 46 +/- 19% vs. 31 +/- 22% in NE. In the skin of healthy controls, only 23 +/- 25 % of the mast cells were positive for IL-4. In addition, a significant difference was found between lesional skin of AD vs. NE patients (P < 0.008, unpaired t-test). Moreover, the staining intensity of IL-4 in mast cells was clearly increased in the lesional compared with the non -lesional AD skin. Mast cells appeared to be the main cell type contai ning IL-4 in 40% of the lesional AD skin specimens, whereas in the rem aining 60% prominent IL-4-positive mononuclear cell infiltrates were a lso present. In the non-lesional skin, mast cells appeared to be the m ain cell type containing IL-4 in all specimens. These results indicate that mast cells are one major source of IL-4 in lesional and non-lesi onal AD skin, and they could contribute significantly to the developme nt of AD.