Demonstration of the Therapeutic Potential of Non-Anaphylactogenic Anti-IgE Antibodies in Murine Models of Skin Reaction, Lung Function and Inflammation

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Abstract
Background: Allergies and allergic asthma are believed to be mediated by allergen-specific IgE antibodies. We have investigated the therapeutic potential of inhibiting endogenous IgE by a non-anaphylactogenic anti-mouse IgE antibody 1–5 with respect to its effects on antigen-induced skin reaction, lung function changes and lung inflammation in mice. Methods: Mice were immunized with benzylpenicillinoyl-KLH or ovalbumin, and antigen-mediated skin reaction, bronchoconstriction, bronchopulmonary hyperresponsiveness (BHR) and lung eosinophilic inflammation determined in anti-IgE 1–5-treated versus untreated animals. Results: Application of anti-IgE 1–5 inhibited (by 90%) the serum IgE and, 3–4 days after onset of treatment, blocked the antigen-induced skin reaction. Furthermore, the antibody also inhibited (by 90%) the antigen-induced infiltration of eosinophils into the lung. This latter effect seems to be mediated by blocking the IgE-CD23 interaction and indicates that lung eosinophilic inflammation also depends on IgE. Moreover, when applied to rats passively sensitized with mouse IgE, antibody 1–5 inhibited the antigen-induced bronchoconstriction. A similar effect could be seen in actively immunized mice, where antibody 1–5 was able to inhibit (by 70%) the ovalbumin-induced bronchoconstriction as well as BHR. Conclusions: In summary, non-anaphylactogenic anti-IgE antibodies can markedly inhibit IgE levels and IgE-mediated allergic reactions. Since bronchoconstriction, BHR and lung eosinophilic inflammation can be suppressed, such antibodies may be attractive principles for the treatment of allergic asthma.

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