Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients

Abstract

Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index > 40 kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23 ± 9.80 years), HOMA-IR (6.74 ± 1.62), total cholesterol (219.7 ± 9.58 mg/dl), aspartate aminotransferase (36.25 ± 3.24 UI/l), gamma-glutamyl transpeptidase (37.12 ± 3.41 UI/l), and TNF-α (37.41 ± 1.72 pg/ml) as well as decreased serum levels of IL-10 (61.05 ± 2.43 pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

“…Other studies have shown in parallel that the reduction, dysfunction, or disproportionate number of Treg cells contributes to the progression to NASH because Treg cells play a critical role in regulating the inflammatory processes in the liver (24, 29, 30). This cellular imbalance is accompanied by the activation of the IL-17 axis, and an increase of other pro-inflammatory cytokines such as IL-6, and TNF-α (42, 58); and its value has been highlighted by the demonstration that therapies targeted to reverse this imbalance have shown the potential to alleviate steatosis and the progression to NASH (32, 61, 62). …”

“…The NAFLD immune imbalances, in addition to the above, appears to be also associated with deficient synthesis or release of anti-inflammatory and antifibrotic cytokines as IL-10 (58, 61), IL-4 (61, 123), IL-22 (42), and interferon gamma (IFN-γ) (124) that have a protective effect by suppressing the maturation of Th17 cells or counterbalancing the IL-17 effects (42, 61, 125–127). For example, Treg requires IL-10 signaling to suppress the Th17 cell-mediated inflammation (100), and this anti-inflammatory cytokine was decreased in morbidly obese patients with NAFLD (58).…”

“…For example, Treg requires IL-10 signaling to suppress the Th17 cell-mediated inflammation (100), and this anti-inflammatory cytokine was decreased in morbidly obese patients with NAFLD (58). Figure 1 shows a simply proposed model connecting the cellular to cytokines imbalances, including the activation of the IL-17 and the progression of NAFLD.…”

Relación de la hiperuricemia con las lipoproteínas de baja densidad, las pruebas de funcionamiento hepático y los marcadores de inflamación sistémica en pacientes con obesidad mórbida

“…En este contexto, se ha demostrado que los pacientes con hiperuricemia asintomática tienen valores elevados de marcadores proinflamatorios, incluyendo IL-6, IL-1 beta e IL-18 4,6 . Sin embargo, hasta la fecha se desconoce si el AU guarda la misma relación con marcadores proinflamatorios y antiinflamatorios en la población mexicana, y si esta relación está vinculada con otras alteraciones metabólicas, así como con un mayor riesgo de desarrollar hipertensión arterial sistémica, DM2, SMet y EHGNA [19][20][21][22][23][24] .…”

The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease

“…TNF could bind to trimerized TNF receptor type I and activate NF-B via the inhibitor of the nuclear factor kappa-B kinase (IKK) pathway. TNF- could induce c-Jun N-terminal kinase (JNK) activation, which is associated with the induction of hepatocyte death (31,32). On the other hand, Lv and his colleagues (33) found that TNF- could directly induce lipid accumulation through the AMP-activated protein kinase (AMPK) pathway, which is known as an important factor in the process of energy homeostasis.…”