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elevations in circulating Th22 cells, Th17 cells, Th1 To date, two cytokines have achieved Food and Drug
cells, IL-22, IL-17A, and IFN-γ were observed in the Administration approval as single agents for cancer
hepatic fibrosis groups compared with the control treatment: high-dose, bolus IL-2 for metastatic
group. [97] melanoma and renal cell carcinoma and IFN-α for the
adjuvant therapy of Stage III melanoma. [103]
It has been demonstrated that the proinflammatary
IL-6 and IL-10 have been implicated to associate The classical and current view of the cytokines role
with certain human cancers and HCC. Previous study and mechanisms in both healthy and diseased liver is
indicated that both IL-6 and IL-10 levels were elevated presented in Figure 6. [104]
in HCC patients compared to normal controls, and
the high levels would invariably decrease after SUMMARY AND CONCLUSION
[98]
surgical resection. In addition, a high IL-10 level
predicted a poor disease-free survival in patients Cytokines are a large family of small proteins secreted
undergoing curative surgery. Hsia et al. found by leukocytes and having an essential role in mediating
[99]
[98]
that both IL-6 and IL-10 expression were more often the immune function. Many cytokines have multiple
higher in HCC patients compared to patients in other cellular sources and targets, as well as many natural
disease categories. inducers and inhibitors. Cytokines are produced to
control body metabolism, infection, inflammation
It has been postulated that an imbalance between and tissue or neuronal damage. The pharmacological
Th1 and Th2 cytokine production is implicated in agents that can either suppress the production of the
disease progression or inability to clear infections. It cytokines or block its biological actions may have
was reported that HCV-infected patients who develop potential therapeutic value against a wide variety
chronicity have a predominant Th2 response, but of liver diseases. However, a stress is needed for
a weak Th1 response, suggesting that this immune a better knowledge about the adverse side effects
response imbalance can result from HCV interaction for the anti-cytokine agents on the autoimmune
with dendritic cell functions. [100] These results support responses; therefore future studies, leading to a
the notion that Th-lymphocyte polarization may play combination of drugs that modulate the cellular
an important pathophysiologic role in influencing the immunity system but selectively block cytokines
outcome of HCV infection. All these immunological action, may be more useful for use to overcome the
findings are mostly due to HCV infection rather than side effects of anti-cytokine therapy in the long-term.
schistosomal infection, because patients with no Again, proinflammation and prooxidation is the main
schistosomal antibody had the same elevation of cause of the complications of various inflammatory
the same cytokines, late Schistosoma mansoni cases diseases. Since the high levels of cytokines directly
showed a suppressed cell-mediated immunity and a induces the oxidative stress of the cells by depleting
significant depletion of T-helper/inducer subset. [101] the vital antioxidant substances (such as glutathione)
of the body and therefore elevate the ROS levels
In the majority of cases, HCC is found in conjunction of the cells, it would be interesting to check the
with cirrhosis of the liver. Chronic inflammation and effectiveness of combination of drugs including
cirrhosis, accompanied by regenerative process, antioxidant enhancer to effectively combat the side
function as a tumor promoter, providing a common effects of anti-cytokine therapy.
pathway from chronic HBV or HCV-infection to HCC.
The direct etiologic role of HBV and HCV for HCC Financial support and sponsorship
is obscure. Tumor progression may be brought Nil.
about in HCC by mutation of p53 tumor suppressor
gene. The prevalence of p53 mutations is similar in Conflicts of interest
HBV-associated and HCV-associated HCCs. Other There are no conflicts of interest.
mechanisms of host defense are the production of REFERENCES
TGF-β1, and the induction of cytotoxic T lymphocytes;
the failure of these mechanisms permits the process 1. Guven-Maiorov E, Acuner-Ozbabacan SE, Keskin O, Gursoy A,
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Cancers (Basel) 2014;6:663-83.
or prevent the progression to liver cirrhosis and 2. Ai W, Li H, Song N, Li L, Chen H. Optimal method to stimulate
development of HCC. [102] cytokine production and its use in immunotoxicity assessment. Int J

140 Hepatoma Research | Volume 2 | June 1, 2016