Efficacy of Tumor Necrosis Factor and Interleukin-10 Analysis in the Follow-up of Nonalcoholic Fatty Liver Disease Progression

Zahran, Walid E.; El-Dien, Kholoud A. Salah; Kamel, Philip G.; El-Sawaby, Ahmed Shawky

doi:10.1007/s12291-012-0236-5

Cited by 35 publications

(34 citation statements)

References 39 publications

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“…Rats genetically deficient for the TNF-α receptor were resistant to develop NASH. 24,26,36 Obesity is an inflammation state characterized by pro-inflammatory cytokines increased levels as TNFα and interleukin-1 beta (IL-1β). In this regard, exists a lack of studies in hepatic tissue about the role of TNFα receptor 1 (TNFR1) in the context of obesity and insulin resistance during NAFLD progression.…”

Section: Discussionmentioning

confidence: 99%

Role of cytokines in pathogenesis and progression of nonalcoholic steatohepatitis

Miranda-Henriques¹,

Carlos²,

Trigueiro³

et al. 2019

GHOA

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Section: Discussionmentioning

confidence: 99%

Role of cytokines in pathogenesis and progression of nonalcoholic steatohepatitis

Miranda-Henriques¹,

Carlos²,

Trigueiro³

et al. 2019

GHOA

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“…In this regard, data from clinical studies and animal models have shown that there is an increased production of pro-inflammatory cytokines, such as, TNF in ALD/NAFLD, while there is decreased activity of the anti-inflammatory cytokine, IL-10 [4, 53–55]. It has also been shown that the imbalance between TNF and IL-10 increases with the progression of the disease from simple hepatic steatosis to steatohepatitis and fibrosis [53, 56–58]. Our earlier work documented that decreased cAMP levels played a causal role in the priming of monocytes/macrophages leading to an increase in LPS-inducible TNF expression [50].…”

Section: Discussionmentioning

confidence: 99%

Misoprostol modulates cytokine expression through a cAMP pathway: Potential therapeutic implication for liver disease

Gobejishvili

Ghare

Khan³

et al. 2015

Clinical Immunology

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Dysregulated cytokine metabolism plays a critical role in the pathogenesis of many forms of liver disease, including alcoholic and non-alcoholic liver disease. In this study we examined the efficacy of Misoprostol in modulating LPS-inducible TNFα and IL-10 expression in healthy human subjects and evaluated molecular mechanisms for Misoprostol modulation of cytokines in vitro. Healthy subjects were given 14 day courses of Misoprostol at doses of 100, 200, and 300 µg four times a day, in random order. Baseline and LPS-inducible cytokine levels were examined ex vivo in whole blood at the beginning and the end of the study. Additionally, in vitro studies were performed using primary human PBMCs and the murine macrophage cell line, RAW 264.7, to investigate underlying mechanisms of misoprostol on cytokine production. Administration of Misoprostol reduced LPS inducible TNF production by 29%, while increasing IL-10 production by 79% in human subjects with no significant dose effect on ex vivo cytokine activity; In vitro, the effect of Misoprostol was largely mediated by increased cAMP levels and consequent changes in CRE and NFκB activity, which are critical for regulating IL-10 and TNF expression. Additionally, chromatin immunoprecipitation (ChIP) studies demonstrated that Misoprostol treatment led to changes in transcription factor and RNA Polymerase II binding, resulting in changes in mRNA levels. In summary, Misoprostol was effective at beneficially modulating TNF and IL-10 levels both in vivo and in vitro; these studies suggest a potential rationale for Misoprostol use in ALD, NASH and other liver diseases where inflammation plays an etiologic role.

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“…We used IL-4 −/− and double IL-10 −/− /IL-4 −/− mice, which were previously shown to develop increasingly polarized type 1 inflammation after sterile or infectious challenge (18,19). Our goal with the IL-10 −/− /IL-4 −/− mice was to assess extreme type 1 inflammatory skewing rather than the specific contribution of IL-10 to NAFLD, which remains unclear despite being previously studied (20)(21)(22)(23)(24)(25). The single IL-10 −/− mice, in contrast to the IL-10 −/− /IL-4 −/− mice, develop more of a mixed T helper cell 1 (T H 1)/T H 2 response when challenged with various inflammatory stimuli, which may, in part, explain the contradictory results regarding IL-10 in NAFLD (18,19).…”

Section: Type 1 Immunity Drives Metabolic Disease But Regulates Progrmentioning

confidence: 99%

Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-β

et al. 2017

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Nonalcoholic fatty liver disease (NAFLD) is now the most common progressive liver disease in developed countries and is the second leading indication for liver transplantation due to the extensive fibrosis it causes. NAFLD progression is thought to be tied to chronic low-level type 1 inflammation originating in the adipose tissue during obesity; however, the specific immunological mechanisms regulating the progression of NAFLD-associated fibrosis in the liver are unclear. To investigate the immunopathogenesis of NAFLD more completely, we investigated adipose dysfunction, nonalcoholic steatohepatitis (NASH), and fibrosis in mice that develop polarized type 1 or type 2 immune responses. Unexpectedly, obese interleukin-10 (IL-10)/IL-4-deficient mice (type 1-polarized) were highly resistant to NASH. This protection was associated with an increased hepatic interferon-γ (IFN-γ) signature. Conversely, IFN-γ-deficient mice progressed rapidly to NASH with evidence of fibrosis dependent on transforming growth factor-β (TGF-β) and IL-13 signaling. Unlike increasing type 1 inflammation and the marked loss of eosinophils seen in expanding adipose tissue, progression of NASH was associated with increasing eosinophilic type 2 liver inflammation in mice and human patient biopsies. Finally, simultaneous inhibition of TGF-β and IL-13 signaling attenuated the fibrotic machinery more completely than TGF-β alone in NAFLD-associated fibrosis. Thus, although type 2 immunity maintains healthy metabolic signaling in adipose tissues, it exacerbates the progression of NAFLD collaboratively with TGF-β in the liver.

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Efficacy of Tumor Necrosis Factor and Interleukin-10 Analysis in the Follow-up of Nonalcoholic Fatty Liver Disease Progression

Cited by 35 publications

References 39 publications

Role of cytokines in pathogenesis and progression of nonalcoholic steatohepatitis

Role of cytokines in pathogenesis and progression of nonalcoholic steatohepatitis

Misoprostol modulates cytokine expression through a cAMP pathway: Potential therapeutic implication for liver disease

Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-β

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