Life sciences · 2021
Etanercept attenuates immune-mediated hepatitis induced by concanavalin A via differential regulation of the key effector cytokines of CD4+ T cells.
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Elshal Mahmoud, Abu-Elsaad Nashwa, El-Karef Amr, Ibrahim Tarek
Аннотация
AIMS: The current study aims to investigate the role of the key effector cytokines produced by CD4+T cells in the pathogenesis of Con A-induced liver injury in mice and testing whether etanercept can be repurposed to differentially regulate these cytokines.
MAIN METHODS: Four groups of mice were used: group I: control group, group II: mice received 15 mg/kg Con A i.v, group III: mice received 15 mg/kg etanercept i.p, group IV: mice received both Con A and etanercept as described. Hepatic injury and necroinflammation were assessed. Infiltration of CD4+ T cells and neutrophils were evaluated. Hepatic levels of TNF-α, IL-4, IL-10, and MDA were assigned and expression of NF-κB as well.
KEY FINDINGS: A significant decrease in ALT, AST, and LDH levels occurred when etanercept was injected before Con A. Hepatic necrosis and infiltration of CD4+ T cells and neutrophils were reduced by etanercept. Levels of TNF-α, IL-4, and MDA were significantly decreased in group IV compared to group II while that of IL-10 was increased. Also, number of NF-κB positive cells was significantly low in group IV.
SIGNIFICANCE: The study elucidates an interplay between the two effector cytokines of CD4+ T cells, TNF-α and IL-4, and their key role in Con A-induced liver injury. Additionally, our results showed that etanercept could be repurposed to differentially regulate effector cytokines produced by CD4+ T cells. Not only TNF-α, but also IL-4 signaling pathways, through which it exerts immunomodulatory, anti-inflammatory, and anti-oxidant effects leading to attenuation of Con A-induced liver injury.
MAIN METHODS: Four groups of mice were used: group I: control group, group II: mice received 15 mg/kg Con A i.v, group III: mice received 15 mg/kg etanercept i.p, group IV: mice received both Con A and etanercept as described. Hepatic injury and necroinflammation were assessed. Infiltration of CD4+ T cells and neutrophils were evaluated. Hepatic levels of TNF-α, IL-4, IL-10, and MDA were assigned and expression of NF-κB as well.
KEY FINDINGS: A significant decrease in ALT, AST, and LDH levels occurred when etanercept was injected before Con A. Hepatic necrosis and infiltration of CD4+ T cells and neutrophils were reduced by etanercept. Levels of TNF-α, IL-4, and MDA were significantly decreased in group IV compared to group II while that of IL-10 was increased. Also, number of NF-κB positive cells was significantly low in group IV.
SIGNIFICANCE: The study elucidates an interplay between the two effector cytokines of CD4+ T cells, TNF-α and IL-4, and their key role in Con A-induced liver injury. Additionally, our results showed that etanercept could be repurposed to differentially regulate effector cytokines produced by CD4+ T cells. Not only TNF-α, but also IL-4 signaling pathways, through which it exerts immunomodulatory, anti-inflammatory, and anti-oxidant effects leading to attenuation of Con A-induced liver injury.