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The goal of this review is to highlight, in brief
account, the major cytokines involved in different
liver damage and discuss their basic biology and
clinical applications.

Cytokines and alcoholic liver disease
Alcohol-related liver disease (ALD) is a major cause of
morbidity and mortality worldwide. Chronic alcohol
consumption leads to hepatocellular injury, fat
accumulation, and liver inflammation and sometimes
leads to liver cirrhosis or hepatocellular carcinoma
(HCC) [Figure 5]. In the liver, TNF-α is mainly
[16]
[17]
produced by KC. The role of TNF-α as a critical
inflammatory cytokine in the progression of ALD is
well known. KC secrete inflammatory cytokines
[18]
[19]
and reactive oxygen species (ROS) which activate
[20]
cells such as hepatocytes, HSCs, and endothelial
cells. After chronic alcohol consumption, KC exhibit
[21]
enhanced sensitivity to lipopolysaccharide (LPS)
[22]
-stimulated TNF-α production. Elevated serum
levels of TNF-α inducible cytokines or chemokines,
including IL-6, IL-8, and IL-18, have also been reported
in patients with alcoholic hepatitis. Serum TNF-α
[23]
is increased in patients with ALD and correlates with
mortality. Treatment with pentoxifylline (an inhibitor
of TNF-α synthesis) improved the survival of patients
Figure 3: Interleukin 1 (IL-1) antagonism: IL-1 activity at the receptor may be with severe alcoholic hepatitis (AH). Anti-TNF-α
[24]
blocked either by (a) competitive inhibition by IL-1 receptor antagonist (IL-1ra)
or by (b) soluble forms of the type II receptor that bind to free IL-1 antibody, infliximab, is also effective in severe AH
patients. These results suggest that TNF-α plays
[25]
of α and β in the circulation. Additionally, cellular
an important role in the progression of ALD.
receptors for both IL-1 and tumor necrosis factor
(TNF) exist in soluble forms, after being cleaved from IL-6 appears to have some beneficial effects on the
liver. IL-6 may protect against hepatocyte apoptosis
the cell surface, and are able to bind and neutralize and participates in mitochondrial DNA repair after

the cytokine [Figure 4]. [15] alcoholic liver injury. IL-6 may promote human
[26]

Figure 4: Maintained activity by soluble interleukin 6 receptor (sIL-6R); ligation of IL-6 with its membrane binding protein (IL-6R) results in association of the complex
with a 130 kDa signal transduction glycoprotein (gp130). When cleaved from the cell surface, the IL-6/sIL-6R complex remains able to bind and activate gp130

134 Hepatoma Research | Volume 2 | June 1, 2016