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

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.

High Frequency of Gamma Interferon-Producing PLZFloRORγtloInvariant Natural Killer 1 Cells Infiltrating Herpes Simplex Virus 1-Infected Corneas Is Associated with Asymptomatic Ocular Herpesvirus Infection

“…This suggests a pathogenic role of IL-6 in HSV-1-infected symptomatic corneas, with a yet-to-be-determined immunopathological mechanism. IL-6 and the related family members IL-1, IL-8, IL-18, IL-33, and TNF-␣ (CXCL8) are the prototype cytokines associated with inflammatory responses to many infectious diseases (76)(77)(78)(79)(80)(81). During early HSV-1 infection, IL-6 can be produced by many immune and nonimmune cells, including mononuclear phagocytes, DCs, endothelial cells, and fibroblasts, in the symptomatic cornea.…”

Mucosal-Resident T Lymphocytes with Invariant Antigen Receptors

“…There is ample evidence that in the lungs of mice iNKT cells carry out protective immune responses to infectious agents; some examples include the bacterium S. pneumoniae (Kinjo et al, 2011;Kawakami et al, 2003), fungi such as A. fumigatus (Albacker et al, 2013;Cohen et al, 2011), and influenza virus (De Santo et al, 2008;Ho et al, 2008). iNKT cells are also protective in diminishing lung fibrosis induced by bleomycin , but they are key participants in worsening pathogenesis in mouse models of chronic obstructive pulmonary disease Pichavant et al, 2013), models of acute lung injury (Shiga et al, 2014), ischemiareperfusion injury (Wallace et al, 2009), and lung remodeling induced in IL-25 transgenic mice (Kawashima et al, 2013).…”

Type 1 invariant natural killer T cells in chronic inflammation and tissue fibrosis

“…•It should be emphasized that iNKT cells may have a protective role during initial acute inflammation (42)(43)(44)(45)(46) whereas chronic activation of iNKT cells may induce a more pathogenic role. Therefore, murine models that are generally acute in nature may not accurately reflect the role of iNKT cells in human chronic conditions such as lung or liver fibrosis.…”