Therapeutic interference with interferon-gamma (IFN-gamma) and soluble IL-4 receptor (sIL-4R) in allergic diseases.

Abstract

Allergic sensitization is controlled by CD4+ T cells. A complex interaction between antigen-presenting cells, T- and B-cells results in the production of (allergen) specific IgE. Analysis of the lymphokine profile of lymphocytes from patients with bronchialasthma and atopic dermatitis revealed an imbalance in cytokine production. An enhanced production of IL-4 was accompanied by low or absent amounts of IFN-gamma. Since both cytokines play a central role in the regulation of IgE, it was examined whether therapeutic interference on the level of cytokine production may provide an useful tool to alter lymphocyte functions in allergic diseases. Two different model systems were employed to study the effects of soluble IL-4R (sIL-4R) under in vitro and in vivo conditions. (1) A mouse model system for allergic sensitization and increased airways responsiveness (AR) was employed to examine whether in vivo treatment with recombinant murine sIL-4R may prevent the development of allergic sensitization. It was found that local treatment through the airways and the lung as carried out by aersolization of the receptor offered a route of application that prevented the development of allergen-induced and allergen-dependent immediate hypersensitivity responses including the development of increased AR. (2). The in vitro effects of humans sIL-4R on functions of mononuclear cells prepared from two patients with most severe atopic dermatitis were examined. Incubation of lymphocytes with allergens in the presence and absence of sIL-4R indicated that the soluble receptor suppressed allergen-induced lymphocyte proliferation and allergen-dependent IgE, IgG and IgM production. In addition a complete suppression of allergen-specific IgE production was detected in the presence of sIL-4R. These data suggest that sIL-4R may provide a useful drug to modify lymphocyte-dependent immune functions in allergic diseases.