IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis.
BACKGROUND
The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH.


METHODS
Steatohepatitis was induced by feeding wild-type or IL-6(-/-) mice for 5 weeks with a methionine and choline-deficient (MCD) diet.


RESULTS
Whereas MCD diet-induced weight loss and decreases in serum glucose, cholesterol and triglyceride levels were similar in both genotypes, serum alanine aminotransferase was less elevated in IL-6(-/-) mice than in wild-type animals. Despite having a comparable liver steatosis score, IL-6-deficient mice exhibited less lobular inflammation than their wild-type littermates. Liver gene expression of TGF-beta and MCP-1 was also strongly attenuated in mutant mice; a more modest reduction was observed for PPAR-gamma and F4/80 transcripts as well as proteins. Chromatographic analysis of liver lipids demonstrated that MCD diet induced in normal and mutant mice a similar decrease in the ratio of phosphatidylcholine to phosphatidylethanolamine. However, the diet-induced increase in the levels of sphingomyelin and ceramide was less important in IL-6(-/-) mice.


CONCLUSIONS
Altogether, these results indicate that IL-6 deficiency does not block the development of NASH; yet, IL-6 plays a critical role in the accompanying liver inflammation.
Mas
Emmanuel
E
INSERM, U858, Toulouse, France.
Danjoux
Marie
M
Garcia
Virginie
V
Carpentier
Stéphane
S
Ségui
Bruno
B
Levade
Thierry
T
D000821:Animal Feed; D000818:Animals; D017209:Apoptosis; D002794:Choline / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics*; D007249:Inflammation; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000378:metabolism
D015850:Interleukin-6; D047495:PPAR gamma; D008715:Methionine; D002794:Choline