Effects of omalizumab on markers of inflammation in patients with allergic asthma.
Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E (IgE) plays a key role by activating a variety of inflammatory cells through interactions with FcepsilonRI and FcepsilonRII receptors. The role of IgE in allergic inflammation provided the rationale for developing omalizumab, a humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or severe allergic asthma. The reductions in circulating levels of IgE resulting from omalizumab treatment leads to reductions in FcepsilonRI expression on mast cells, basophils and dendritic cells. This combined effect results in attenuation of several markers of inflammation, including peripheral and bronchial tissue eosinophilia and levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its receptors and diminishing dendritic cell FcepsilonRI receptor expression, omalizumab may also reduce allergen presentation to T cells and the production of Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore, explain the reductions in asthma exacerbations and symptoms seen in clinical trials in patients with moderate-to-severe or severe, persistent, inadequately controlled allergic asthma.
Southampton General Hospital, Southampton, UK.
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S
Holgate
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Smith
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M
Massanari
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Jimenez
D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy*; D000069444:Omalizumab
D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000069444:Omalizumab