Eosinophils confer protective benefit in acetaminophen-induced acute liver injury

Hepatic recruitment of eosinophils appears to play a protective role during acute liver injury caused by acetaminophen overdose, reveals a recent study.

“This is the first study to demonstrate that hepatic recruitment of and protection by eosinophils occur commonly in various models of acute liver injury,” the authors said.

“The data demonstrate that IL-33-activated eosinophils trigger macrophages to release high amounts of eotaxin-2 (CCL24), which promotes hepatic eosinophil recruitment,” they explained.

The authors detected and quantified hepatic eosinophils using flow cytometry and immunohistochemical staining. They used eosinophil-deficient mice to examine the role of eosinophils in three models of acute liver injury.

Finally, in order to explore the mechanism of CCL24 production, the authors performed in vivo experiments using Il33^-/- mice and macrophage-depleted mice, as well as in vitro cultures of eosinophils and macrophages.

Patients with acetaminophen-induced liver failure demonstrated hepatic accumulation of eosinophils, but few eosinophils were observed in healthy liver tissues.

In mice treated with acetaminophen, carbon tetrachloride, or concanavalin A, eosinophils were recruited into the liver and found to play a protective function. In mice deficient of macrophages or IL-33, hepatic recruitment of eosinophils was impaired during acute liver injury.

Moreover, CCL24, but not CCL11, showed an increase following treatment of each hepatotoxin in an IL-33 and macrophage-dependent manner. In vitro experiments demonstrated how IL-33 induced the production of CCL24 by macrophages through the stimulation of IL-4 release from eosinophils.

“The current study unveils that eosinophils are recruited into the liver and play a protective function during acute liver injury caused by acetaminophen overdose,” the authors said. “Our findings suggest that eosinophils could be an effective cell-based therapy for the treatment of acetaminophen-induced acute liver injury.”