Differential Cytokine Profiles in Peripheral Blood Lymphocyte Supernatants and Skin Biopsies from Patients with Different Forms of Atopic Dermatitis, Psoriasis and Normal Individuals

Abstract

There is increasing evidence that the activation of a selected T helper cell population producing a Th2-related cytokine pattern with IL-4 and IL-5 but no IL-2 and interferon-γ (IFN-γ) may be involved in the pathogenesis of IgE-mediated atopic diseases and in particular of atopic dermatitis (AD). However, the existence of a ‘nonatopic’ (intrinsic) form of AD (NAD) with normal serum IgE levels, negative RAST tests, negative immediate type skin reactions towards environmental allergens and a negative patients and family history for IgE-mediated allergies raised the question whether this form may be explained by a different T cell activation and cytokine pattern. In the present study we compared the distribution of peripheral blood leukocyte and lymphocyte subpopulations, their activation state and cytokine production in peripheral blood lymphocyte supernatants and skin biopsies of patients with AD (n = 19), NAD (n = 14) psoriasis (n = 6) and normal individuals (n = 13). A characteristic eosinophilia was present in AD and NAD but not in psoriasis and normal controls. The three patient groups showed significantly increased numbers of activated CD4+ and CD8+ cells as measured by IL-2R and HLA-DR expression. Determination of spontaneously released IL-2, IL-4, IL-5 and IFN-γ from peripheral blood lymphocytes demonstrated a Th2-related cytokine pattern with elevated levels for IL-4 and IL-5 in AD patients only. Interestingly enough, patients with NAD displayed high IL-5 but low IL-4 levels. In order to further investigate the possible cytokine involvement in these diseases, supernatants obtained from mechanically disrupted lesional skin biopsies were analyzed for the presence of the above mentioned cytokines. Again, only in skin biopsies obtained from patients with AD significantly increased levels of IL-4 could be demonstrated. In contrast, IL-5 was significantly elevated in the skin of AD and NAD patients. When comparing lesional to nonlesional skin, significantly lower levels of IL-5 were observed in the nonlesional skin biopsies for all patient groups. For IL-2 and IFN-γ no significant differences were found among the various populations. In conclusion, our data defining differential skin cytokine profiles extend knowledge about cytokine-mediated inflammatory processes in the skin of AD and NAD patients and further support the concept of basic immunological differences between AD and NAD.