The immunoprotective activity of interleukin-33 in mouse model of cecal ligation and puncture-induced sepsis

Abstract

Lymphocyte apoptosis plays a pivotal role in sepsis-induced immunosuppression and is the primary cause of high mortality rates. Interleukin-33 is a member of the interleukin-1 family that is involved in the polarization of T cells toward a T helper 2-cell phenotype and may regulate apoptotic cell death. The objective of the present study was to assess the effects of interleukin-33 on T lymphocyte apoptosis in sepsis and determine the mechanisms involved. Sepsis was induced in C57BL/6 mice via a cecal ligation and puncture. Mice were infused with recombinant interleukin-33 protein at 1h and 6h after surgery. The mortality rates were evaluated over the subsequent 7 days. In a separate experiment, mice were sacrificed 24h after surgery. Bacterial burdens in the blood and peritoneal cavity were calculated to assess the bacterial clearance. Liver, lung and renal pathology were observed via transmission electron microscopy. The serum levels of interleukin-6, interleukin-10, interleukin-17, interferon-γ and tumor necrosis factor-α were measured via enzyme-linked immunosorbent assays. The number of T and B lymphocytes, the percentage of apoptotic cells and the expression of Fas, Bcl-2, caspase-3, caspase-8 and caspase-9 in CD3(+) T lymphocytes were analyzed by flow cytometry. Interleukin-33 enhanced bacterial clearance, attenuated the severity of organ damage and improved the survival of septic mice. Interleukin-33 decreased the levels of interleukin-6, interleukin-10, interferon-γ and tumor necrosis factor-α, and it increased the levels of interleukin-17. Interleukin-33 also inhibited the apoptosis of CD4(+) and CD8(+) T lymphocytes and CD19(+) B cells in the spleen. The number of CD3(+) T cells was higher and the expression of active caspase-3, caspase-8 and caspase-9 was lower in the interleukin-33 group compared to the CLP group. The expression of Fas was lower and the expression of Bcl-2 was higher in the interleukin-33 group than in the CLP group. Interleukin-33 prevented apoptosis of T lymphocytes and improved survival in a mouse model of sepsis.

Keywords: Apoptosis; Interleukin-33; Sepsis; T lymphocyte.