Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy

Int Arch Allergy Immunol. 2010;151(4):275-84. doi: 10.1159/000250436. Epub 2009 Oct 22.


Background: Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair, 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anti-Asthmatic Agents / administration & dosage*
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Asthma / blood
  • Asthma / drug therapy*
  • Asthma / immunology
  • Basophils / drug effects*
  • Basophils / immunology
  • Basophils / metabolism
  • Basophils / pathology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Follow-Up Studies
  • Histamine Release / drug effects
  • Humans
  • Male
  • Middle Aged
  • Omalizumab
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism*


  • Anti-Asthmatic Agents
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • FcepsilonRI alpha-chain, human
  • Receptors, IgE
  • Omalizumab