Serum levels of cytokines and adipokines in patients with non-alcoholic steatohepatitis and type 2 diabetes mellitus

Background: Non-alcoholic steatohepatitis (NASH) - the severe form of non-alcoholic fatty liver disease (NAFLD) - diagnosed by liver biopsy, was associated with the risk of rapid progression of cardiovascular disease, in several large longitudinal studies. Although the pathogenesis of NASH remains poorly understood, proinflammatory cytokines seem to play an important role in the process of NASH. The aim of this study was to assess the chronic systemic inflammatory profile (i.e., proinflammatory cytokines IL-6, IL-1ß, and TNF-a), hs-CRP, and the anti-inflammatory profile (i.e., serum adiponectin) in patients with type 2 diabetes mellitus (DMT2) and NASH. Materials and methods: A total of 117 participants (32 patients with NASH (diagnosed by liver biopsy) and DMT2; 45 patients with DMT2 only; and 40 controls) were included in the present study. The serum levels of a panel of markers of chronic systemic inflammation (tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and adiponectin) were measured by the enzyme-linked immunosorbent assay (ELISA) method. Results: Patients with NASH and DMT2, in comparison with patients with DMT2 only, exhibited significantly higher serum levels of IL-6 (134.83 ± 57.18 pg/ml vs. 55.68 ± 18.29 pg/ml, p = 0.001), IL-lß (73.45 ± 15.11 pg/ml vs. 22.07 ± 9.17 pg/ml, p = 0.001), and TNF-a (60.88 ± 12.31 pg/ ml vs. 18.81 ± 7.25 pg/ml, p = 0.021). In contrast to the increase of proinflammatory cytokine concentrations, the serum level of adiponectin in patients with NASH and DMT2 was found lower than in patients with DMT2 only (3950.5 ± 954 ng/ml vs. 6745 ± 1122 ng/ml, p = 0.002), and controls. Moreover, regarding the hs-CRP, this parameter of chronic systemic inflammation was found significantly elevated in patients with NASH and DMT2 (8.4 ± 5.9 mg/l) compared to patients with DMT2 only (4.72 ± 3.6 mg/l) and controls (2.11 ± 1 mg/l) (p=0.001). The results of correlation analyses revealed a number of significant interactions between the proinflammatory cytokines, antiinflammatory adipocytokines, and hs-CRP, with multiple clinical and biochemical patient characteristics. Conclusions: Overall, this study's evidence indicates that the serum levels of IL-6, IL-1ß, TNF-a, and hs-CRP are significantly increased in patients with NASH and DMT2, and the serum levels of adiponectin are decreased in this population.