IL-33 deficiency attenuated sepsis-induced lung injury at early stage

Author(s):

Meihong Deng; Timothy Billiar; Li Xu

Background:

Acute lung injury (ALI) develops at early stage in sepsis and remains a major clinical problem with high morbidity and mortality, with the exact mechanisms remains to be elucidated.

Hypothesis:

In this study, we aimed to investigate the role of endogenous IL-33 in sepsis-induced ALI.

Methods:

We assessed the effects of IL-33 deficiency on lung histopathology, leukocytes infiltration, ILC2s propagation and cytokine production in the early phase of sepsis.

Results:

We demonstrated that IL-33 deficiency attenuated sepsis-induced lung injury by suppressing infiltration of PMNs and pulmonary monocytes, and by reducing TNF-α, IL-1β, IFN-γ and IL-10 productions from these cells. IL-33^-/- mice has a defect in IL-5-producing ILC2s and IL-5 release. Treatment of IL-33^-/- mice with recombinant IL-5 led to revived infiltration of PMNs and pulmonary monocytes in the lungs, while neutralization of IL-5 in wide-type mice resulted in reduced numbers of these cells.

Conclusions:

These results suggested the role of IL-33–IL-5 axis in mediating sepsis-induced lung injury.