A protective role of interleukin 11 on hepatic injury in acute endotoxemia.

Overview

The liver is one of the major target organs affected in sepsis, and its failure always results in critical consequences. It has been reported that recombinant human interleukin 11 (rhIL-11), a pleiotropic cytokine, may be useful in the treatment of sepsis. However, the effect of IL-11 specifically on the hepatic failure in sepsis has not been evaluated. In the present study, we examined the effect of rhIL-11 on the hepatic injury in a rat endotoxemia model. Acute endotoxemia was induced in male Sprague-Dawley rats by intraperitoneal injection (i.p.) of bacterial lipopolysaccharide (LPS, 20 mg/kg). Immediately after injection of LPS, rats were treated with rhIL-11 (150 microg/kg, i.p.) or the vehicle. LPS treatment induced severe hepatic injury as revealed by marked increases in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, extensive hepatocyte necrosis, tumor necrosis factor-alpha (TNF-alpha) mRNA, inducible nitric oxide synthase (iNOS) mRNA, and DNA-binding activity of nuclear factor-kappaB (NF-kappaB). In contrast, rhIL-11 treatment significantly ameliorated the LPS-induced hepatic injury, as judged by marked improvement in all these indices. In addition, rhIL-11 treatment markedly decreased LPS-induced mortality. These results indicate that rhIL-11 plays a significant protective role in LPS-induced hepatic injury in acute endotoxemia.