Immunomodulators for allergic respiratory disorders.
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 gamma, and nuclear factor kappaB 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.
Casale
Thomas B
TB
Department of Medicine, Division of Allergy/Immunology, Creighton University, Omaha, NE 68131, USA. tbcasale@creighton.edu
Stokes
Jeffrey R
JR
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000209:etiology; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D006967:Hypersensitivity / Q000150:complications*; D007073:Immunoglobulin E / Q000276:immunology; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D012120:Respiration Disorders / Q000188:drug therapy* / Q000209:etiology*; D051193:Toll-Like Receptors / Q000819:agonists; D014157:Transcription Factors / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D053264:B-Cell Activating Factor; D016207:Cytokines; D007155:Immunologic Factors; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors; D014157:Transcription Factors; D007073:Immunoglobulin E