Cytokines and Liver Diseases

Abstract

Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a) has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

IL‐12 and IL‐15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells

“…This may mimic events in vivo in which an inflammatory hepatic cytokine microenvironment, found in hepatitis or cancer, dominated by IL‐1, IL‐2, IL‐6, IL‐12, IL‐15, IL‐18, IFNα, IFNγ, and TNFα/β 38, 39, may lead to the expansion of CD49a+ NK cells. Of the three patients in our cohort with significant enrichment of hepatic CD49a+ NK cells, one had hepatocellular carcinoma, one had aggressive colorectal cancer with synchronous lesions and bi‐lobar liver metastases and the third had colorectal metastases extending to the resection margins, suggesting that high frequencies of CD49a+ NK cells are associated with more severe liver disease.…”

MyD88-Dependent Recruitment of Monocytes and Dendritic Cells Required for Protection from Pulmonary Burkholderia mallei Infection

“…For example, MyD88 Ϫ/Ϫ mice are known to have defects in liver regeneration (26). Additional defects in MyD88 Ϫ/Ϫ mice may also contribute to liver damage, as other cytokines in addition to TNF-␣ are known to elicit liver damage and suppress effective regeneration (5,6,25,28).…”

Viral and Host Factors Induce Macrophage Activation and Loss of Toll-Like Receptor Tolerance in Chronic HCV Infection

“…TNFα, a potent inducer of inflammation and a key regulator of innate immunity, is beneficial for generation of the initial immune responses against viruses, including HCV (22). However TNFα has multiple harmful effects including induction of hepatocyte apoptosis, aggravation of liver fibrosis, and increase in the frequency of autoimmune diseases associated with HCV (23,24). Increased production of TNFα in T cells, NK, NKT cells and dendritic cells of cHCV-infected hosts was previously reported and may play a detrimental role in HCV clearance (6,22,25).…”