Upon prolonged allergen exposure IL-4 and IL-4R alpha knockout mice produce specific IgE leading to anaphylaxis

Background: IL-4 and IL-13 are key regulators in atopic disorders and both signal through the receptor chain IL4R alpha. IL-4 and IL-13 are also the o nly cytokines known to induce class switching to IgE. We sought to compare allergen-specific IgE responses and allergic reactivity of wild-type (wt) m ice with IL-4(-/-) and IL-4R alpha (-/-) mice, which lack both IL-4 and IL- 13 functions. Methods: BALB/c wt, IL-4(-/-) and IL-4R alpha (-/-) mice were immunized with ovalbumin intranasally or intraperitoneally and specific an tibody titers were measured by ELISA. Bronchoalveolar lavage fluids and lun g tissue were analyzed cytologically and histologically. Allergic reactivit y was determined by active cutaneous anaphylaxis and anaphylactic shock. Re sults: wt mice immunized intranasally or intraperitoneally showed high tite rs of specific IgE 3 and 6 weeks after primary sensitization, resulting in cutaneous anaphylaxis and anaphylactic shock upon challenge. Intranasal sen sitization resulted in airway eosinophilia and goblet cell metaplasia. In c ontrast, IL-4(-/-) and IL-4R alpha (-/-) mice showed no specific IgE after 3 weeks, but produced high titers after 6 weeks. At this time cutaneous ana phylaxis and anaphylactic shock could be induced as in wt mice, but lung pa thology was absent. Conclusions: We conclude that upon long-term allergen e xposure, alternative switch mechanisms independent of IL-4 and IL4R alpha m ay induce IgE but not asthma-like lung pathology. This may be relevant for the development of allergic disease, since long-term allergen exposure is a frequent condition during allergic sensitization. Copyright (C) 2001 S. Ka rger AG, Basel.