| Title | Reduced FcepsilonRI-Mediated Release of Asthma-Promoting Cytokines and Chemokines from Human Basophils during Omalizumab Therapy. | | Author(s) | Oliver JM, Tarleton CA, Gilmartin L, Archibeque T, Qualls CR, Diehl L, Wilson BS, Schuyler M | | Institution | Department of Pathology, University of New Mexico School of Medicine, Albuquerque, N. Mex., USA. | | Source | Int Arch Allergy Immunol 2009 Oct 22; 151(4):275-284. | | Abstract | Background: Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair(R)), reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, FcepsilonRI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the FcepsilonRI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined.
Methods: Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests.
Results: Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release.
Conclusions: Omalizumab may reduce asthma symptoms in part by suppressing the FcepsilonRI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of FcepsilonRI caused by omalizumab treatment. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19844128 |
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