title: Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2.
abstract: 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.
authors.affiliation: Faculty Division, Aker University Hospital, University of Oslo, Oslo, Norway. j.w.haukeland@medisin.uio.no
authors.forename: John Willy
authors.initials: JW
authors.lastname: Haukeland
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Konopski
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.forename: Terese
authors.initials: T
authors.lastname: Haaland
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Goverud
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torjesen
authors.forename: Kåre
authors.initials: K
authors.lastname: Birkeland
authors.forename: Kristian
authors.initials: K
authors.lastname: Bjøro
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: 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
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines