In drug-induced, immune-mediated hepatitis, interleukin-33 reduces hepatitis and improves survival independently and as a consequence of FoxP3+ T-cell activity.

Cellular & Molecular Immunology
Merylin CottagiriDolores B Njoku

Abstract

Immune-mediated, drug-induced hepatitis is a rare complication of halogenated volatile anesthetic administration. IL-4-regulated Th2-polarized reactions initiate this type and other types of hepatitis, while the mechanisms that regulate the severity remain elusive. IL-33 is an innate, IL-4-inducing, Th2-polarizing cytokine that has been detected in patients with liver failure and has been associated with upregulated ST2+Foxp3+CD4+CD25+ T cells; however, roles for IL-33 in drug-induced hepatitis are unclear. We investigated IL-33 in an anesthetic, immune-mediated hepatitis modeled in BALB/c, IL-33-/- and ST2-/- mice, as well as in patients with anesthetic hepatitis. The hepatic IL-33 and ST2 levels were elevated in BALB/c mice (p < 0.05) with hepatitis, and anti-IL-33 diminished hepatitis (p < 0.05) without reducing IL-33 levels. The complete absence of IL-33 reduced IL-10 (p < 0.05) and ST2+Foxp3+CD4+CD25+ T cells (p < 0.05), as well as reduced the overall survival (p < 0.05), suggesting suppressive roles for IL-33 in anesthetic, immune-mediated hepatitis. All of the mice demonstrated similar levels of CD4+ T-cell proliferation following direct T-cell receptor stimulation, but we detected splenic IL-33 and ST2-negative Foxp3+CD...Continue Reading

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Citations

Jan 4, 2020·Journal of Pediatric Gastroenterology and Nutrition·Norman Junge
Jun 5, 2019·Cellular & Molecular Immunology·Lu WangLi Bai
Dec 4, 2019·Frontiers in Immunology·Meijuan Zheng, Zhigang Tian
Oct 13, 2020·Cellular & Molecular Immunology·Zhongming Tan, Beicheng Sun
Jan 1, 2021·Microbial Pathogenesis·Hilal Ahmad KhanMuhammad Imran Arshad
May 1, 2021·International Journal of Molecular Sciences·Alessio GerussiPietro Invernizzi

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Methods Mentioned

BETA
ELISA
flow cytometry
FCS

Software Mentioned

GraphPad
nCounter
GraphPad Prism

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