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Immunol Cell Biol. 2018 Oct;96(9):935-947. doi: 10.1111/imcb.12159. Epub 2018 May 17.

Interleukin-33 contributes to ILC2 activation and early inflammation-associated lung injury during abdominal sepsis.

Author information

1
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
2
Department of Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
3
State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
4
Department of Emergency, Union Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan, 430022, China.
5
Department of Anesthesia, Shanghai East Hospital, Tongji University, Shanghai, 200120, China.

Abstract

Sepsis is defined as infection with organ dysfunction due to a dysregulated immune response. The lung is one of the most vulnerable organs at the onset of sepsis. Interleukin (IL)-33 can be released by injured epithelial and endothelial cells in the lung and regulate immune activation and infiltration. Therefore, we postulated that IL-33 would contribute to the immune response in the lung during sepsis. Using the cecal ligation and puncture (CLP) sepsis model, we show here that IL-33 contributes significantly to both sepsis-induced inflammation in the lung and systemic inflammatory response in the early phase of sepsis. Despite the higher intra-peritoneal bacterial burden, the absence of IL-33 resulted in less infiltration of neutrophils and monocytes into the lungs in association with lower circulating, lung and liver cytokine levels as well as reduced lung injury at 6 h after sepsis. IL-33 was required for the upregulation of IL-5 in type 2 Innate Lymphoid Cells (ILC2), while IL-5 neutralization suppressed neutrophil and monocyte infiltration in the lungs during CLP sepsis. This reduction in leukocyte infiltration in IL-33-deficient mice was reversed by administration of recombinant IL-5. These results indicate that IL-33 plays a major role in the local inflammatory changes in the lung, in part, by regulating IL-5 and this axis contributes to lung injury early after the onset of sepsis.

KEYWORDS:

interleukin-33; lung; sepsis

PMID:
29672927
DOI:
10.1111/imcb.12159
[Indexed for MEDLINE]

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