Effect of invariant natural killer T cells with IL-5 and activated IL-6 receptor in ventilator-associated lung injury in mice

Yuka Shiga, Ryuichi Sugamata, Chiaki Iwamura, Tomokazu Nagao, Jun Zao, Kazuyoshi Kawakami, Shoji Kawachi, Toshinori Nakayama, Kazuo Suzuki

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Mechanical ventilation (MV) is well known to potentially cause ventilator-associated lung injury (VALI). It has also been reported recently that activation of invariant natural killer T (iNKT) cells is involved in the onset/progression of airway inflammation. We analyzed the roles of inflammatory cells, including iNKT cells, and cytokines/chemokines in a mouse model of VALI. C57BL/6 and Vα14+NKT cell-deficient (Jα18KO) female mice were subjected to MV for 5 hours. The MV induced lung injury in the mice, with severe histological abnormalities, elevation in the percentages of neutrophils in the bronchoalveolar lavage fluid (BALF), and increase in the number of iNKT cells in the lung. Jα18KO mice subjected to MV for 5 hours also showed lung injury, with decrease of the PaO2/FiO2 ratio (P/F ratio) and elevation of the levels of total protein, IL-5, IL-6, IL-12p40, and keratinocyte-derived cytokine (KC) in the BALF. Intranasal administration of anti-IL-5 monoclonal antibody (mAb) or anti-IL-6 receptor (IL-6R) mAb into the Jα18KO mice prior to the start of MV resulted in significant improvement in the blood oxygenation. In addition, the anti-IL-5 mAb administration was associated with a decrease in the levels of IL-5, IL-9, and IL-6R in the BALF, and anti-IL-6R mAb administration suppressed the mRNA expressions of IL-5, IL-6, IL-6R, and KC. These results suggest that iNKT cells may play a role in attenuating the inflammatory caused by ventilation through IL-5 and IL-6R.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalExperimental Lung Research
Volume40
Issue number1
DOIs
Publication statusPublished - 2014 Feb
Externally publishedYes

Keywords

  • IL-5
  • IL-6 receptor
  • Invariant NKT cell
  • Ventilator-associated lung injury

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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