Cytoprotection by interleukin-6 against liver injury induced by lipopolysaccharide.
The role of interleukin (IL)-6 in inflammatory injury remains controversial. The present study elucidated the role of IL-6 in liver damage during severe inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS; 1 mg/kg) using IL-6 null (-/-) mice and corresponding wild-type (WT) mice. Histological study showed that LPS treatment caused more severe liver injury with centrilobular vacuolation of hepatocytes and neutrophilic infiltration in the liver of IL-6 (-/-) mice; in contrast, neutrophilic infiltration and mild vacuolar change of hepatocytes were found in the liver of LPS-treated WT mice. Protein levels of proinflammatory molecules, such as IL-1beta, macrophage inflammatory protein-1alpha, and macrophage chemoattractant protein-1, in the livers were significantly greater in IL-6 (-/-) mice than in WT mice after LPS challenge. These results directly indicate that IL-6 is protective against liver injury induced by bacterial endotoxin, at least partly, via the modulation of proinflammatory cytokines and chemokines.
Inoue
Ken-Ichiro
K
Pathophysiology Research Team, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Takano
Hirohisa
H
Shimada
Akinori
A
Morita
Takehito
T
Yanagisawa
Rie
R
Sakurai
Miho
M
Sato
Masahiko
M
Yoshino
Shin
S
Yoshikawa
Toshikazu
T
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004731:Endotoxins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D022781:Hepatocytes / Q000378:metabolism; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides