Rationale for new treatments aimed at IgE immunomodulation.
OBJECTIVE
To review potential or current therapies that decrease IgE synthesis or effects.


METHODS
Relevant literature in peer-reviewed journals and abstracts from national meetings.


METHODS
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 TH1 phenotype, thus decreasing TH2-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 TH1 and inhibiting TH2 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 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.
Division of Allergy/Immunology, Department of Medicine, Creighton University, Omaha, Nebraska 68131, USA.
Jeffrey
J
Stokes
Thomas B
TB
Casale
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001190:Arylsulfonates / Q000627:therapeutic use; D018899:CpG Islands; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects; D015316:Genetic Therapy; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016233:Immunotherapy, Active; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000069444:Omalizumab; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D017455:Receptors, IgE / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D013452:Sulfonium Compounds / Q000627:therapeutic use; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000819:agonists / Q000502:physiology; D000098815:T-bet Transcription Factor
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001190:Arylsulfonates; D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007166:Immunosuppressive Agents; D007378:Interleukins; D018160:Receptors, Cytoplasmic and Nuclear; D017455:Receptors, IgE; D013452:Sulfonium Compounds; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; C026408:anti-IgE antibodies; D000069444:Omalizumab; D007073:Immunoglobulin E; C073028:suplatast tosilate