Neutrophils exacerbate acetaminophen-induced liver injury by producing cytotoxic interferon-γ.

ABSTRACT:

Background

Drug (e.g., acetaminophen, APAP)-associated hepatotoxicity is the major cause of acute liver failure. Emerging evidence shows that initial tissue damage caused by APAP triggers molecular and cellular immune responses, which can modulate the severity of hepatoxicity. The pro-inflammatory and cytotoxic cytokine interferon (IFN)-γ has been reported as a key molecule contributing to APAP-induced liver injury (AILI). However, its cellular source remains undetermined.

Results

In the current study, we show that elevation of serum IFN-γ in patients with drug hepatotoxicity correlates with disease severity. Neutralization of IFN-γ in a mouse model of AILI effectively reduces hepatotoxicity. Strikingly, we reveal that IFN-γ is expressed primarily by hepatic neutrophils, not

SUBMITTER: Wu H 

PROVIDER: S-EPMC10603570 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature