RESEARCH PAPER
Proinflammatory cytokines (IL-6, IL-18) and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis
1
Department of Internal Medicine, Medical University of Lublin, Poland
2
Department of Family Medicine, Medical University of Lublin, Lublin, Poland
3
Department of Ethics and Human Philosophy, Medical University of Lublin, Poland
4
Department of Nephrology, Medical University of Lublin, Poland
5
Department of Ophthalmology, Poznań City Hospital, Poznań, Poland
6
Chair of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland
7
Department of Medical Chemistry, Medical University of Lublin, Lublin, Poland
8
Department of Mathematics and Medical Biostatistics, Medical University of Lublin, Lublin
9
Individual Medical Practice, Lublin, Poland
Corresponding author
J Pre Clin Clin Res. 2017;11(1):1-5
KEYWORDS
ABSTRACT
Introduction:
Apoptosis is involved in the pathogenesis of alcoholic liver cirrhosis. Its development can be triggered by an inflammatory process. In the present study, levels of apoptotic factors – survivin human protein p53 (HP 53) and IL-6, IL-18 were determined according to the stage of liver cirrhosis.
Material and Methods:
Seventy patients with alcoholic liver cirrhosis, treated in various hospitals of the Lublin region, Poland were included in the study. Serum levels of IL-6, IL-18, HP53 and survivin were determined by the enzyme-linked immunosorbent assay (ELISA) technique.
Results:
The serum level of survivin in patients with alcoholic liver cirrhosis was not statistically different from that found in the control group. The level of HP53 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (16.53±22.69 vs. 0.39±1.31 U/ml; p<0.001). Likewise, the level of IL-6 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (33.83±41.78 vs. 0.88 ± 0.56 pg/ml; p<0.001). Moreover, the level of IL-18 was significantly higher in the group of patients with liver cirrhosis compared to the control group (23.96±31.07 vs. 5.3±8.6 pg/ml; p<0.001).
Conclusions:
In conclusion, increased serum levels of IL-6 and IL-18 were demonstrated in patients with alcoholic liver cirrhosis. Moreover, the liver cirrhosis patients had elevated levels of HP53, which is a marker of apoptosis. Our results did not demonstrate the correlation between the levels of apoptosis markers (survivin, HP53) and the levels of cytokines (IL-6, IL-18) in the blood serum.
Apoptosis is involved in the pathogenesis of alcoholic liver cirrhosis. Its development can be triggered by an inflammatory process. In the present study, levels of apoptotic factors – survivin human protein p53 (HP 53) and IL-6, IL-18 were determined according to the stage of liver cirrhosis.
Material and Methods:
Seventy patients with alcoholic liver cirrhosis, treated in various hospitals of the Lublin region, Poland were included in the study. Serum levels of IL-6, IL-18, HP53 and survivin were determined by the enzyme-linked immunosorbent assay (ELISA) technique.
Results:
The serum level of survivin in patients with alcoholic liver cirrhosis was not statistically different from that found in the control group. The level of HP53 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (16.53±22.69 vs. 0.39±1.31 U/ml; p<0.001). Likewise, the level of IL-6 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (33.83±41.78 vs. 0.88 ± 0.56 pg/ml; p<0.001). Moreover, the level of IL-18 was significantly higher in the group of patients with liver cirrhosis compared to the control group (23.96±31.07 vs. 5.3±8.6 pg/ml; p<0.001).
Conclusions:
In conclusion, increased serum levels of IL-6 and IL-18 were demonstrated in patients with alcoholic liver cirrhosis. Moreover, the liver cirrhosis patients had elevated levels of HP53, which is a marker of apoptosis. Our results did not demonstrate the correlation between the levels of apoptosis markers (survivin, HP53) and the levels of cytokines (IL-6, IL-18) in the blood serum.
REFERENCES (32)
1.
Tsujimoto T, Kawaratani H, Yoshiji H, Uemura M, Fukui H: Recent developments in the treatment of alcoholic chronic pancreatitis. Curr Drug Abuse Rev, 2008; 1: 197–202.
2.
Tsujimoto T, Kuriyama S, Yamazaki M et al: Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers. Int J Oncol. 2001; 18: 41–7.
3.
Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ: Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest. 2003; 83: 655–63.
4.
Nanji AA, Hiller-Sturmhöfel S: Apoptosis and necrosis: two types of cell death in alcoholic liver disease. Alcohol Health Res World. 1997; 21: 325–30.
5.
Ghavami S, Hashemi M, Kadkhoda K, Alavian SM, Bay GH, Los M: Apoptosis in liver diseases – detection and therapeutic applications. Med SciMonit. 2005; 11: RA337–45.
6.
Kania J, Konturek SJ, Marlicz K, Hahn EG, Konturek PC: Expression of survivin and caspase-3 in gastrin cancer. Dig Dis Sci. 2003; 48: 266–71.
7.
Yang H, Du X, Xi Y: Effects of survivin on FVADT chemotherapy for refractory multiple myeloma. ExpTher Med. 2016; 12: 771–76.
8.
Pan Y, Xing Y, Wang H: Expression of survivin in adenoid cystic carcinoma of the lacrimal gland and the effect of intervention with arsenic trioxide in vitro. ExpTher Med. 2015; 10: 330–4.
9.
He XJ, Zhang Q, Ma LP, Li N, Chang XH, Zhang YJ: Aberrant Alternative Polyadenylation is Responsible for Survivin Up-regulation in Ovarian Cancer. Chin Med J. 2016; 129: 1140–6.
10.
Liu Y, Teng Z, Wang Y, Gao P, Chen J:Prognostic Significance of Survivin Expression in Osteosarcoma Patients: A Meta-Analysis. Med SciMonit. 2015; 21:2877–85.
11.
Peroukides S, Bravou V, Alexopoulos A, Varakis J, Kalofonos H, Papadaki H:Survivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin. HistolHistopathol. 2010; 25: 299–307.
12.
Jia X, Gao Y, Zhai D et al:Survivin is not a promising serological maker for the diagnosis of hepatocellular carcinoma. Oncol Lett. 2015; 9: 2347–52.
13.
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW: Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991; 51: 6304–11.
14.
Hainaut P, Wiman K: 30 years and long way into p53 research. Lancet Oncol. 2009; 10: 913–9.
15.
Zaika AI, El-Rifai W: The role of p53 protein family in gastrointestinal malignancies. Cell Death Differ. 2006; 13: 935–40.
16.
Jackson PE, Qian GS, Friesen MD et al: Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry. Cancer Res, 2001; 61: 33–5.
17.
Zhang Q, Ma S, Liu B, Liu J, Zhu R, Li M:Chrysin induces cell apoptosis via activation of the p53/Bcl-2/caspase-9 pathway in hepatocellular carcinoma cells. ExpTher Med, 2016; 12: 469–74.
18.
Minouchi K, Kaneko S, Kobayashi K: Mutation of p53 gene in regenerative nodules in cirrhotic liver. J Hepatol, 2002; 37: 231–9.
19.
Shahnazari P, Sayehmiri K, Minuchehr Zet al: The Increased Level of Serum p53 in Hepatitis B-Associated Liver Cirrhosis. Iran J Med Sci, 2014; 39: 446–51.
20.
Attallah AM, Shiha GE, Ismail H, Mansy SE, El-Sherbiny R, El-Dosoky I: Expression of p53 protein in liver and sera of patients with liver fibrosis, liver cirrhosis or hepatocellular carcinoma associated with chronic HCV infection. ClinBiochem, 2009; 42: 455–61.
21.
Gracie JA, Robertson SE, McInnes IB: Interleukin-18. J LeukocBiol 2003; 73: 213–24.
22.
Montoliu C, Piedrafita B, Serra MAet al.: IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy. J ClinGastroenterol, 2009; 43: 272–9.
23.
Jia H, Du J, Zhu S, Ma Y, Cai H: Clinical observation of serum IL-18, IL-10 and sIL-2R levels in patients with chronic hepatitis C pre- and post antiviral treatment. Chin Med J, 2003; 116: 605–8.
24.
Zhou G, Zhou Z, Ge Set al: IL-18 accelerates the cell apoptosis by up-regulating cysteinyl leukotriene 2 receptor expression in human umbilical vein endothelial cells at the early stage of administration. VasculPharmacol, 2009; 50: 171–7.
25.
Ludwiczek O, Kaser A, Novick D et al.: Plasma levels of interleukin-18 and interleukin-18 binding protein are elevated in patients with chronic liver disease. J ClinImmunol, 2002; 22: 331–7.
26.
Lichtenstein A, Tu Y, Fady C, Vescio R, Berenson J: Interleukin-6 inhibits apoptosis of malignant plasma cells. Cell Immunol, 1995; 162: 248–55.
27.
Wei ST, Sun YH, Zong SH, Xiang YB: Serum Levels of IL-6 and TNF-α May Correlate with Activity and Severity of Rheumatoid Arthritis. Med SciMonit. 2015;21:4030–8.
28.
Song Z, Lin Y, Ye X et al: Expression of IL-1α and IL-6 is Associated with Progression and Prognosis of Human Cervical Cancer.Med SciMonit, 2016;22:4475–81.
29.
Deviere J, Content J, Denys C et al: High interleukin-6 serum levels and increased production by leucocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production. ClinExpImmunol, 1989; 77: 221–5.
30.
Lee FY, Lu RH, Tsai YT et al: Plasma interleukin-6 levels in patients with cirrhosis. Relationship to endotoxemia, tumor necrosis factor-alpha, and hyperdynamic circulation. Scand J Gastroenterol, 1996; 31: 500–5.
31.
Persson J, Berg NO, Sjölund K, Stenling R, Magnusson PH: Morphometric changes in the small intestine after chronic alcohol consumption. Scand J Gastroenterol, 1990; 25: 173–84.
32.
Floch MH, Katz J, Conn HO. Qualitative and quantitative relationship of the faecal flora in cirrhotic patients with portal systemic encephalopathy and following portocaval anastomosis. Gastroenterology, 1970; 59: 70–5.
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