Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma - 20/08/11
, Gerald Hanf, MD a, Ilka Brachmann, MD a, Andrea C. Klucken, MD a, Jörg Kleine-Tebbe, MD b, Simone Rosseau, MD a, Gert Kunkel, MD a, b, Norbert Suttorp, MD a, Joachim Seybold, MD a
Reprint requests: Oliver Noga, MD, Department of Internal Medicine, Respiratory and Infectious Diseases, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.Berlin, Germany
Abstract |
Background |
Omalizumab is a recombinant monoclonal anti-IgE antibody with proven efficacy in allergic diseases and further anti-inflammatory potency in the treatment of asthma.
Objectives |
To explore the anti-inflammatory mechanism of omalizumab, we investigated the induction of immunologic changes leading to eosinophil apoptosis and examined T-lymphocyte cytokine profiles in patients with allergic asthma.
Methods |
Nineteen patients with allergic asthma were enrolled and received omalizumab at a dose of at least 0.016 mg/kg/IgE (IU/mL) every 4 weeks. Peripheral eosinophils and T-lymphocyte cytokine profiles were evaluated by fluorescence-activated cell sorting before treatment (baseline), at 12 weeks of treatment, and 12 weeks after discontinuation of treatment with omalizumab or placebo.
Results |
Markers of eosinophil apoptosis (Annexin V) were significantly increased in omalizumab recipients compared with placebo, whereas no changes in markers of necrosis (7-amino-actinomycin) or eosinophil activation CD69 or Fas receptor (CD95) were detected. GM-CSF+ lymphocytes were reduced in omalizumab recipients compared with placebo. Fewer IL-2+ and IL-13+ lymphocytes were evident in omalizumab recipients than in the placebo group. There were no significant differences in IL-5, IFN-γ, or TNF-⍺ between the omalizumab and placebo groups.
Conclusion |
These findings provide further evidence that omalizumab has additional anti-inflammatory activity demonstrated by induction of eosinophil apoptosis and downregulation of the inflammatory cytokines IL-2 and IL-13. Further studies are needed to determine the underlying mechanisms.
Clinical implications |
These findings support the critical role of IgE in the regulation of inflammation in allergic asthma: influencing the inflammation is the key to control the more severe type of asthma.
Le texte complet de cet article est disponible en PDF.Key words : Omalizumab, allergic asthma, asthma treatment, inflammation, anti-IgE, eosinophils, T-lymphocytes
Abbreviations used : 7AAD, APC
Plan
| Supported by Novartis Pharma Germany. Disclosure of potential conflict of interest: O. Noga, G. Hanf, A. Klucken, S. Rosseau, G. Kunkel, N. Suttorp, and J. Seybold have all received a grant from Novartis Pharma. The rest of the authors have declared that they have no conflict of interest. |
Vol 117 - N° 6
P. 1493-1499 - juin 2006 Retour au numéro
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