Effects of lnterferon-Alpha-2b on the Clinical Course, Inflammatory Skin Infiltrates and Peripheral Blood Lymphocytes in Patients with Severe Atopic Eczema

Abstract

Increased serum IgE and enhanced susceptibility to viral infections, decreased levels of interferons, lymphocytic skin infiltrates and IgE-bearing epidermal Langerhans cells are striking features in patients with atopic eczema (AE). Since the hyper-IgE syndrome is known to improve under α-interferon (α-IFN) therapy, we treated 7 patients with severe AE and high serum IgE exclusively with 3 × 10⁶ units IFNα2b thrice weekly for 3 months. Before treatment the skin infiltrates mainly consisted of CD3+/CD4+/TcRα/β+ lymphocytes, whereas the CD3+/CD8+ phenotype was limited to about 10% of cells. After 6 weeks of therapy, epidermal inflammation with CD4+ and CD8+ cells was reduced but dense infiltrates remained in papillary perivascular areas. Expression of TcRγ/δ, HLA-DR and CD25 showed no significant changes. Initially high serum IgE and soluble CD23 as well as cell-bound IgE dropped under therapy, whereas a short-term elevation in serum IL-2 receptor was observed. On peripheral blood lymphocytes slightly reduced expression of HLA-DR, LFA-1, CD23 and ICAM-1 was seen after 100 days. LFA-3 expression became reduced in 4 patients, the CD4/CD8 ratio decreased in all cases. After an initial therapeutic response of all patients, significant longer-lasting improvement of the skin lesions could only be observed in 2 of 7 patients. The data of our long-term study suggest that systemic IFNα2b treatment leads to a remarkable reduction in epidermal inflammation but does not significantly influence cutaneous cell subsets. Immunomodulatory effects became obvious by reduced peripheral cell subsets expressing TcRα/β, MHC class II and adhesion molecules.

Atopic Phenotype in Children Is Associated with Decreased Virus-Induced Interferon-α Release

“…Consequently, the application of IFN-αA2 in an animal model of asthma led to a reduction in allergic inflammation and asthmatic symptoms. In humans, antiallergic treatment with IFN-α has been tested only in single cases and especially in atopic dermatitis [17, 18, 19]. Until now, it has not been proven to be generally effective in these diseases.…”

Recombinant interferon-alpha selectively inhibits the production of interleukin-5 by human CD4+ T cells.

“…Recombinant IFN-␣ therapy has been successfully used in diseases characterized by accumulation of eosinophils such as the hypereosinophilic syndrome (1-3) and atopic dermatitis (4,5). In these disorders, IFN-␣ might act directly on eosinophils by inhibiting their differentiation and proliferation (6) as well as their recruitment into tissues (7).…”

Total Serum IgE Levels in Chronic Hepatitis C: Influence of Interferon Alpha Therapy

“…Previous studies of the effect of IFN-α on atopic diseases and serum IgE levels gave conflicting results [19, 20, 21, 22, 23, 24, 25, 26, 27, 28](table 4). The cause of this discrepancy is not clear but could be related to differences in the age of the patients studied, the associated diseases, the dose administered, and the type of IFN-α used.…”

“…The cause of this discrepancy is not clear but could be related to differences in the age of the patients studied, the associated diseases, the dose administered, and the type of IFN-α used. Clinical response to IFN-α in atopic dermatitis or hyper-IgE syndrome ranged from marked improvement [19, 20, 21]to moderate benefit [22, 23, 24], no change [25, 27]or even worsening [26]of skin lesions. The most striking improvement was reported by Kimata et al [21]after administration of large doses of natural IFN-α therapy to children.…”

“…Influencing the profile of cytokines could be a useful strategy for the treatment of immune diseases [13], including IgE-mediated disorders. In small series of patients, IFN-α therapy offered conflicting results concerning both the reduction of serum IgE levels and the clinical improvement of atopic diseases [19, 20, 21, 22, 23, 24, 25, 26, 27, 28]. The effect of IFN-α on IgE levels in nonatopic adult patients has not been tested.…”