Rationale for new treatments aimed at IgE immunomodulation

Objective: To review potential or current therapies that decrease IgE synthesis or effects. Data Sources: Relevant literature in peer-reviewed journals and abstracts from national meetings. Study Selection: Key articles were selected by the authors. Results: Modulation of IgE-mediated diseases can occur at several levels. Transcription factors may be altered to differentiate lymphocytes into a T_H1 phenotype, thus decreasing T _H2-driven IgE production. This may be accomplished by inhibiting GATA-3 with peroxisome proliferator-activated receptor agonists or promoting T-bet expression with CpG motifs. Inhibiting IgE-promoting cytokines may be accomplished by blocking the effects or synthesis of interleukin 4 (IL-4) or IL-13 by suplatast tosilate. Cytokine therapy with anti-IL-4 or anti-IL-13 has the potential to directly influence IgE-mediated diseases, but strategies aimed at IL-4 alone have been disappointing. Clinical trials with interferon-γ or IL-12, 2 cytokines important in promoting T_H1 and inhibiting T_H2 responses, have been fraught with adverse effects that make their use limited. The use of plasmids encoding interferon-γ or IL-12 has shown promise in animal models. Inhibition of IgE synthesis has been demonstrated with anti-CD23 antibodies. Early human studies have been very encouraging, and larger studies are under way. The only IgE immunomodulator currently available for use is omalizumab. Omalizumab is effective for allergic asthma in children and adults. Conclusions: Newer therapies hold great promise for the future treatment of allergic respiratory diseases, but clinical trials are necessary to accurately evaluate risk-benefit ratios of IgE immunomodulators.