Rationale for new treatments aimed at IgE immunomodulation

被引:39
作者
Stokes, J [1 ]
Casale, TB [1 ]
机构
[1] Creighton Univ, Dept Med, Div Allergy Immunol, Omaha, NE 68131 USA
关键词
D O I
10.1016/S1081-1206(10)61490-1
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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(H)1 phenotype, thus decreasing T(H)2-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-gamma or IL-12, 2 cytokines important in promoting T(H)1 and inhibiting T(H)2 responses, have been fraught with adverse effects that make their use limited. The use of plasmids encoding interferon-gamma or IL-12 has shown promise in animal models. Inhibition of I-E 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.
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收藏
页码:212 / 217
页数:6
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