Role of cytokines and chemokines in non-alcoholic fatty liver disease

Table 1 Summary of human studies concerning the role of cytokines and chemokines in non-alcoholic fatty liver disease

Cytokine/chemokine	References	Findings	Approach/sample size	Treatment
TNF-α	Hotamisligil et al[22]	Increase of TNF-α in fat tissue of obese subjects	18 control and 19 obese premenopausal women	-
		Correlation between TNF-α and IR
	Dandona et al[23]	Higher TNF-α levels in obese subjects that contribute to IR	30 control and 38 obese women	-
		Decrease of TNF-α levels and IR with weight loss
	Lesmana et al[24]	Correlation between TNF-α serum levels and liver fibrosis	30 patients with NASH	-
	Crespo et al[25]	Overexpression of TNF-α in liver and adipose tissue in patient with NASH	52 obese patients	-
		Increase of p55 TNF-α receptor expression in fibrotic liver
		Enhancement of TNF-α expression with advanced liver fibrosis
	Hui et al[26]	Increase of TNF-α and TNFR2 in patients with NASH	109 patients with NAFLD	-
	Valenti et al[27]	Higher prevalence of 238 TNF-α polymorphism in patients with NAFLD	99 subjects with NAFLD	-
	Zhou et al[28]	238 TNF-α polymorphism association with NAFLD susceptibility	117 subjects with NAFLD	-
	Lee et al[29]	Reduction of aminotransferase in patients treated with Pentoxifylline	20 patients with NASH	Pentoxifylline 400 mg three time per day
	Müller et al[30]	No significant increase of TNF-α or its receptor levels in patients with IGT	80 subjects with IGT, 152 subjects with type II diabetes and 77 control subjects	-
	Bruun et al[31]	No correlation between IR and TNF-α levels	19 obese and 10 lean men	-
	Ofei et al[32]	No effect on insulin sensitivity	21 obese NIDDM patients	Single injection of CDP571 (anti-TNF-α antibody)
	Bernstein et al[33]	No effect on insulin sensitivity	56 subjects with metabolic syndrome	Etanercept (TNF-α antagonist) 50 mg 1 time per week, for 4 wk
TGF-β1	Annoni et al[40]	Enhancement of TGF-β1 expression in man with active liver disease	16 patients with active liver disease	-
	Castilla et al[44]	Association of TGF-β1 levels and fibrosis in chronic liver disease	46 patients with elevated serum ALT	-
	Milani et al[45]	High TGF-β1 mRNA expression in fibrotic liver	2 subjects control, 1 subject with cirrhosis, and 9 subjects with hepatitis B viral liver disease	-
	Hasegawa et al[47]	TGF-β1 levels are useful to differentiate between NAFLD and NASH Benefits of α-tocopherol to treat NASH	12 patients with non-alcoholic steatohepatitis and 10 patients with non-alcoholic fatty liver	α-tocopherol 300 mg/d during 1 yr
	Dixon et al[48]	Association of polymorphism inducing angiotensinogen and TGF-β1 and advanced hepatic fibrosis	105 obese patients	-
IL-6	Kopp et al[58]	Correlation between IL-6 and IR	37 obese patients	-
	Kugelmas et al[60]	Elevated IL-6 concentration in serum of patients with NASH Decrease of IL-6 with the treatment	16 patients with NASH	Vitamin E 800 IU/d
	Haukeland et al[61]	Higher levels of IL-6 in patients with NAFLD	47 patients (22 simple steatosis, 25 NASH) and 30 controls	-
	Wieckowska et al[63]	Higher hepatic IL-6 expression in patients with NASH Association with IL-6 levels and the disease severity Correlation between hepatic IL-6 expression and IR	50 patients with suspected NALFD
IL-10	Esposito et al[69]	Association between low levels of IL-10 and metabolic syndrome	50 obese and 50 normal-weight women	-
	Calcaterra et al[70]	No association between metabolic syndrome and low levels of IL-10	70 severely obese and 30 non-obese children and adolescents	-
CCL2/MCP-1	Haukeland et al[61]	Elevated levels of CCL2 in patients with NAFLD and NASH	47 patients (22 simple steatosis, 25 NASH) and 30 controls	-
	Westerbacka et al[92]	Increase of CCL2 in steatotic liver of patients with NAFLD	24 subjects (8 controls, 16 with NAFLD)	-
	Greco et al[93]	Correlation between CCL2 gene expression and liver fat content in patients with NAFLD	10 subjects with low and high extremes of fat liver	-
CCL5/RANTES	Wu et al[99]	Higher CCL5 expression in adipose tissue of obese patients than in lean controls	21 morbidly obese patients, 10 obese patients with metabolic syndrome, and 3 lean controls	-
	Kirovski et al[100]	Upregulation of hepatic and circulating CCL5 levels in patients with NAFLD	45 patients with NAFLD and 61 controls with normal liver	-
CXCL8/IL-8	Bahcecioglu et al[103]	Higher serum levels of IL-8 in patients with NASH and cirrhosis compared to control group	28 patients with NASH, 14 patients with cirrhosis, and 15 controls	-
	Torer et al[104]	Higher IL-8 serum levels in the patients with NASH than in patients with hepatosteatosis	57 patients with NASH and 35 patients with NALFD	-
	Jarrar et al[105]	Higher levels of IL-8 in NAFLD patients compared to obese and non-obese subjects	26 patients with NASH, 19 patients with simple steatosis,	-
		Independent association of IL-8 levels with NASH	38 obese controls, and 12 non-obese controls
	Abiru et al[106]	No differences of IL-8 between NASH, simple steatosis, and control groups	23 patients with NASH, 21 patients with simple steatosis, and 18 healthy controls	-
CXCL9/Mig	Wasmuth et al[109]	Association CXCL9 serum levels and CXCL9 liver expression with liver fibrosis due to NASH	441 individuals with HCV

NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steato-hepatitis; TNF: Tumor necrosis factor; TGF: Transforming growth factor; IL: Interleukin; MCP: Monocyte chemotactic protein; RANTES: Regulated on activation normal T-cell expressed and secreted; Mig: Monokine induced by interferon-γ; IR: Insulin resistance; IGT: Impaired glucose tolerance; NIDDM: Noninsulin-dependent diabetes mellitus; ALT: Alanine aminotransferase; HCV: Hepatitis C virus.