Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease

Background & objectives: The cytokines, adipokines, and oxidative stress have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, such data remain scarce in India. The present study evaluated pro-inflammatory cytokines, adipokines, and markers of oxidative stress in patients with non-alcoholic fatty liver disease (NAFLD), and their association with degree of adiposity, insulin resistance and markers of disease severity. Methods: The present prospective cross-sectional pilot study included 79 subjects; 34 NAFLD, 22 chronic hepatitis B (CH-B) and 23 healthy controls (HC). The parameters studied were adiponectin, leptin, tumour necrosis factor alpha (TNF alpha), interleukin-1 and 6 (IL-1, IL-6), and systemic markers of oxidative stress. Results: The mean body mass index (kg/m(2)) in NAFLD patients, CHB, and HC were 26.4 +/- 3.7, 21.3 +/- 2.3, and 22.3 +/- 2.7, respectively. The median serum levels of all pro-inflammatory cytokines were significantly higher (P<0.001) in NAFLD compared to control groups. Compared to HC, levels of adiponectin and leptin were significantly (P<0.05, P<0.01) reduced in both NAFLD and CHB. IL-6 showed marked and selective increase only in NAFLD patients. The levels of IL-6 were significantly (P<0.02) higher in NAFLD patients with advanced histology grade and correlated with IR (r=0.42, P=0.02). In a sub-group, markers of oxidative stress were significantly higher, and that of antioxidant potential were significantly lower among NAFLD patients compared to control subjects. Interpretation & conclusions: Patients with NAFLD revealed significantly elevated levels of pro-inflammatory cytokines, increased oxidative stress, and a significant association of IL-6 with IR and advanced histopathology.