Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2.
OBJECTIVE
To elucidate the role of systemic inflammation in nonalcoholic fatty liver disease (NAFLD).


METHODS
Serum samples in 47 patients with histologically verified NAFLD (22 with simple steatosis and 25 with nonalcoholic steatohepatitis [NASH]), and in 30 age-, sex- and ethnicity-matched healthy controls, were assessed for (i) general markers of inflammation (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6), (ii) chemokines (CC-chemokine ligand [CCL] 2/monocyte chemoattractant protein [MCP]-1, CCL19 and CCL21), (iii) adipocytokines related to insulin resistance and inflammation (adiponectin and leptin) and (iv) a marker of oxidative stress (8-isoprostane-F2alpha).


RESULTS
Serum levels of several inflammatory cytokines were increased in NAFLD as compared to controls, and IL-6 (P=0.017), CCL2/MCP-1 (P=0.008) and CCL19 (P=0.001), but not CRP (P=0.199), remained elevated also after correction for sex, body mass index (BMI) and age. Comparing NASH with simple steatosis, levels of TNF-alpha (P=0.024) and CCL2/MCP-1 (P=0.012) were elevated and adiponectin (in women) (P=0.001) were decreased also after adjustment for sex, BMI and presence of the metabolic syndrome.


CONCLUSIONS
Our results indicate that patients with NAFLD are characterized by a low-grade systemic inflammation. The high CCL2/MCP-1 levels in NASH might be of importance for the conversion from simple steatosis to NASH.
Haukeland
John Willy
JW
Faculty Division, Aker University Hospital, University of Oslo, Oslo, Norway. j.w.haukeland@medisin.uio.no
Damås
Jan Kristian
JK
Konopski
Zbigniew
Z
Løberg
Else Marit
EM
Haaland
Terese
T
Goverud
Ingeborg
I
Torjesen
Peter A
PA
Birkeland
Kåre
K
Bjøro
Kristian
K
Aukrust
Pål
P
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D005234:Fatty Liver / Q000276:immunology* / Q000473:pathology; D005260:Female; D006521:Hepatitis, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015854:Up-Regulation
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines