Immunomodulators for allergic respiratory disorders

• Published in: Journal of allergy and clinical immunology 2008-02, Vol.121 (2), p.288-296
• Main Authors: Casale, Thomas B., MD, Stokes, Jeffrey R., MD
• Format: Article
• Language: English
• Subjects: Accreditation; Allergies; Allergy and Immunology; Antibodies, Monoclonal - therapeutic use; Asthma - drug therapy; Asthma - etiology; B-Cell Activating Factor - antagonists & inhibitors; Biological and medical sciences; Clinical trials; cytokine blockers; Cytokines - antagonists & inhibitors; Deoxyribonucleic acid; Disease; DNA; Drug therapy; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genomes; Human subjects; Humans; Hypersensitivity - complications; Immune system; Immunoglobulin E - immunology; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Immunomodulators; Medical sciences; monoclonal antibodies; Mortality; Pathogenesis; Respiration Disorders - drug therapy; Respiration Disorders - etiology; Respiratory diseases; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Toll-Like Receptors - agonists; transcription factors; Transcription Factors - antagonists & inhibitors
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.11.040

New knowledge about the pathogenesis of allergic and immunologic diseases has led to a variety of novel targeted therapeutic approaches. Many immunomodulators are currently under development for the therapy of asthma and allergic and immunologic diseases and are undergoing human clinical trials. The study of immunomodulators in human subjects is ultimately required to determine their therapeutic utility because several agents showing promise in in vitro and animal models have failed in human studies. Novel therapeutic approaches include Toll-like receptor 4 and 9 agonists, immunostimulatory oligodeoxynucleotides, oral and parenterally administered cytokine blockers, and specific cytokine receptor antagonists. Transcription factor modulators targeting syk kinase, peroxisome proliferator-activated receptor γ, and nuclear factor κB are also being evaluated for the treatment of allergic diseases, especially asthma. The anti-IgE mAb omalizumab is already used for the treatment of allergic asthma, but its potential role for other allergic diseases has yet to be clearly defined. Overall, the development of new agents that inhibit specific immunopathogenic mechanisms holds promise for beneficial outcomes for patients with the least amount of risk. However,agents that are too specific in their targets might not exhibit therapeutic benefits because of the redundancy of the immune system and the heterogeneity of diseases such as asthma. The goal of this review is to summarize the data from human clinical trials with immunomodulators, discussing the rationale for their use, efficacy results, and putative adverse events associated with them.