title: A protective role of interleukin 11 on hepatic injury in acute endotoxemia.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama 700-8558, Japan.
authors.forename: Kyoichiro
authors.initials: K
authors.lastname: Maeshima
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kiichi
authors.initials: K
authors.lastname: Nakahira
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimizu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katayama
authors.forename: Masataka
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Morita
authors.forename: Reiko
authors.initials: R
authors.lastname: Akagi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sassa
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism*; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000473:pathology; D017370:Interleukin-11 / Q000502:physiology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000293:injuries* / Q000382:microbiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D017370:Interleukin-11; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase