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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Immunity, Innate
  • Interleukin-33 / immunology*
  • Interleukin-5 / immunology*
  • Lung / immunology
  • Lymphocytes / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration
  • Pneumonia / immunology*
  • Sepsis / immunology*

Substances

  • Il33 protein, mouse
  • Interleukin-33
  • Interleukin-5