Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells

Journal of Hepatology
Jun YanShulin Li

Abstract

Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation and sepsis-induced death. Sepsis was induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). The inhibitory effects of IL-30 on septic inflammation and associated therapeutic effects were determined in wild-type, IL30 (p28)(-/-), IL10(-/-), and CD1d(-/-) mice. Mice treated with pIL30 gene therapy or recombinant IL-30 protein (rIL30) were protected from LPS-induced septic shock or CLP-induced polymicrobial sepsis and showed markedly less liver damage and lymphocyte apoptosis than control septic mice. The resulting reduction in mortality was mediated through attenuation of the systemic pro-inflammatory response and augmentation of bacterial clearance. Mice lacking IL-30 were more sensitive to LPS-induced sepsis. Natural killer-like T cells (NKT) produced much higher levels of IL-10 and lower levels of interferon-gamma and tumor necrosis factor-alpha in IL-30-treated septic mice than in control septic mice. Likewise,...Continue Reading

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Citations

Aug 11, 2018·Clinical and Molecular Hepatology·UNKNOWN Korean Association for the Study of the Liver (KASL)
Jan 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Stephanie I MüllerMatthias J Feige
Sep 25, 2019·Infection and Immunity·Jeongho ParkChristopher A Hunter
Nov 22, 2016·Frontiers in Immunology·Hideaki HasegawaTakayuki Yoshimoto
May 16, 2018·The Journal of Infectious Diseases·Fang XuJu Cao
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Feb 6, 2020·Frontiers in Immunology·Sofia Noli TruantMarisa M Fernández
Nov 5, 2019·Frontiers in Oncology·Olena KourkoKatrina Gee
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May 29, 2021·Experimental & Molecular Medicine·Booki MinMatthias J Feige
Jun 4, 2021·Frontiers in Immunology·Yugo MoritaGowrishankar Muthukrishnan

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