Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma

  • Shin OhtaEmail author
  • Akihiko Tanaka
  • Megumi Jinno
  • Kuniaki Hirai
  • Yoshito Miyata
  • Munehiro Yamaguchi
  • Tetsuya Homma
  • Mayumi Muramoto
  • Yoshio Watanabe
  • Shintaro Suzuki
  • Takuya Yokoe
  • Hironori Sagara
Sleep Breathing Physiology and Disorders • Original Article



Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity. We investigated whether intermittent hypoxia (IH), which is a physiological feature of OSAS, modifies allergic airway inflammation in a murine model of asthma.


Balb/c mice were sensitized by ovalbumin (OVA) intraperitoneally twice (days 1 and 14) and challenged with intranasal OVA three times (days 21, 22, and 23). The mice were exposed to IH either from days 1 to 24 (long exposure) or only from days 21 to 24 (short exposure). The impact of IH exposure to allergic airway inflammation was investigated using these mice models by histologic, morphometric, and molecular techniques. Additionally, the airway responsiveness to acetylcholine was also assessed.


OVA-sensitized and OVA-challenged mice exposed to room air (RA) showed increased total cell and eosinophil numbers in the BALF. The levels of interleukin (IL)-5 and IL-13 in the BALF also increased and goblet cell metaplasia was induced. In contrast, both long and short exposure to IH inhibited the increased total cell and eosinophil numbers. The levels of IL-5 and IL-13 in the BALF also decreased on exposure to IH. Moreover, the goblet cell hyperplasia and airway hyperresponsiveness were significantly reduced in mice exposed to IH compared to those exposed to RA.


These results suggest that IH may not deteriorate the asthmatic condition in a murine model of asthma.


Allergic airway inflammation Animal model Asthma Intermittent hypoxia Sleep apnea syndrome 



We would like to thank Kyoko Inui and Manami Matsuda for their skillful technical assistance. We would also like to thank Editage ( for English language editing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Shin Ohta
    • 1
    Email author
  • Akihiko Tanaka
    • 1
  • Megumi Jinno
    • 1
  • Kuniaki Hirai
    • 1
  • Yoshito Miyata
    • 1
  • Munehiro Yamaguchi
    • 1
  • Tetsuya Homma
    • 1
  • Mayumi Muramoto
    • 1
  • Yoshio Watanabe
    • 1
  • Shintaro Suzuki
    • 1
  • Takuya Yokoe
    • 1
  • Hironori Sagara
    • 1
  1. 1.Department of Internal Medicine, Division of Respiratory Medicine and AllergologyShowa University School of MedicineTokyoJapan

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