Elimination of eosinophils using anti-IL-5 receptor alpha antibodies effectively suppresses IL-33-mediated pulmonary arterial hypertrophy

Masashi Ikutani*, Shinya Ogawa, Tsutomu Yanagibashi, Terumi Nagai, Kazuki Okada, Yoko Furuichi, Kiyoshi Takatsu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Interleukin (IL)-5 is a critical regulator of eosinophils and a therapeutic target for asthma. The administration of anti-IL-5 or anti-IL-5 receptor (IL-5R) antibodies has been shown to reduce eosinophil counts and ameliorate asthmatic symptoms in studies on animal models of allergy as well as in human clinical trials. In order to explore other potential clinical uses of IL-5R antibodies, we used an animal model of IL-33-mediated pulmonary arterial hypertrophy. We first generated chimeric monoclonal antibodies against the mouse IL-5 receptor α chain (IL-5Rα), which comprised an Fc region from human IgG1 and a Fab region from a previously established anti-mouse IL-5Rα monoclonal antibody. To investigate the role of antibody-dependent cell-mediated cytotoxicity (ADCC), chimeric antibodies that lacked ADCC were prepared. These antibodies recognized IL-5Rα to the same extent as the ADCC-sufficient antibodies. Administration of chimeric antibodies with ADCC resulted in the elimination of eosinophils from the lung and thus suppressed the development of arterial hypertrophy. This effect was attenuated in mice treated with antibodies lacking ADCC. Taken together, the results of this study provided a potential use for anti-IL-5Rα antibodies in the treatment of arterial hypertrophy, which leads to pulmonary hypertension.

Original languageEnglish
Pages (from-to)486-492
Number of pages7
JournalImmunobiology
Volume223
Issue number6-7
DOIs
StatePublished - 2018/06/01

Keywords

  • Eosinophil
  • Immunotherapy
  • Interleukin-33
  • Interleukin-5
  • Pulmonary arterial hypertrophy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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