Immunoregulation in allergy: the potential of anti-IgE antibodies of IL-4 antagonists for the treatment of allergic diseases.

IL-4 plays a crucial role in the induction of allergic responses, not only in inducing the switch of B cells to the production of IgE antibodies but also in promoting the differentiation of T cells to the TH2 phenotype leading to the production of IL-4 and IL-5. Initially, IL-4 may be provided by basophils and/or mast cells which have been shown to produce IL-4 as a consequence of IgE receptor-mediated stimulation. However, after immunization IgE+B cells may persist for a prolonged period leading to further IgE responses which are IL-4-independent. In order to achieve inhibition of IgE, independent of the nature of the allergen and independent of the state of immunization, non-anaphylactogenic anti-IgE antibodies have been generated, which were shown to inhibit IgE in vivo without inducing anaphylactic reactions. A corresponding humanized (mouse-human chimeric) anti-human IgE antibody has been generated in collaboration between Tanox Biosystems and Ciba. This antibody is now under clinical investigation for the potential treatment of allergic rhinitis.