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

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 V alpha 14(+) NKT cell-deficient (J alpha 18KO) 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. Ja18KO mice subjected to MV for 5 hours also showed lung injury, with decrease of the PaO2/FiO(2) 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 Ja18KO 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.