IL-17 deficiency attenuates acetaminophen-induced hepatotoxicity in mice

Area of Science:

• Hepatology
• Immunology
• Toxicology

Background:

• Acetaminophen (APAP) overdose causes liver failure through oxidative stress and necrosis.
• Interleukin-17 (IL-17), a pro-inflammatory cytokine, is implicated in inflammatory damage, including liver ischemia-reperfusion injury.

Purpose of the Study:

• To investigate the role of IL-17 in APAP-induced hepatotoxicity using IL-17 knockout (KO) mice.
• To determine if IL-17 deficiency attenuates liver injury and associated inflammatory responses after APAP overdose.

Main Methods:

• Comparison of APAP-induced liver injury in IL-17 wide type (WT) and IL-17 KO mice.
• Assessment of liver injury markers (ALT, MPO), inflammatory mediators, immune cell infiltration, and ERK signaling pathway activation 16 hours post-APAP injection.

Main Results:

• IL-17 KO mice showed significantly reduced APAP-induced liver injury, MPO activity, and pro-inflammatory cytokine levels compared to WT mice.
• IL-17 deficiency attenuated neutrophil and macrophage infiltration into the liver.
• Phosphorylated ERK levels were decreased in IL-17 KO mice after APAP treatment.

Conclusions:

• IL-17 plays a critical role in mediating APAP-induced hepatotoxicity by modulating inflammatory responses.
• The ERK signaling pathway may be partially involved in IL-17's effect on APAP toxicity.
• Blocking IL-17 presents a potential therapeutic strategy for managing APAP-induced liver injury.