Expressions And Significances Of Cytpokines In Patients With Hepatitis B Virus Infection

【Background】HBV remains one of the most common reasons of hepatic disease, such as acute hepatitis, chronic hepatitis, cirrhosis, liver cancer. The potential mechanisms for viral infection leading to the progression of these diseases remain poorly understood. Some studies showed that the damage of the liver cells in HBV-related liver disease may be not caused by HBV virus directly, but by the cytokines in vivo. Cytokines, released by the actived lymphocyte, lymphatic tissue and other tissues and cells, are lots of small molecular peptides with immunology activities. Cytokines produced by Th1 cells include IFN-γ, IL-2, TNF and so on, whiel cytokine produced by Th2 cell include IL-4,IL-6, IL-10 etc. Previous researches mainly focused on the function of cellular immunity and Th1 cell-related cytokines in HBV infection, but not referred to the Th2 cell-related cytokines. We hypothesized that Th2 cell-related cytokines might also play important roles and serve important values for the diagnosis, treatment and prediction of the HBV-related liver diseases. Cyclooxygenases (COXs) are the key enzymes which regulats the biosynthesis of prostanoids. There are two isoforms of COX: COX-1 is constitutively expressed in various types of cells, while COX-2 is a rate-limiting enzyme involved in the production of prostaglandins (PGs), prostacyclin and thromboxanes. COX-2 is induced in response to a variety of proinflammatory agents and cytokines. Over-expression of COX-2 has been demonstrated in various tumors and chronic inflammatory diseases, such as rheumatoid arthritis and ulcerative colitis. Recent studies have shown that COX-2 and its important product, PGE2, are associated with liver pathogenesis, including hepatitis, fibrosis and cancer. Fulminant hepatitis is a serious disease and mortality rate is high. Prognosis of fluminant hepatitis is influenced by many factors. Glucose-insulin-potassium (GIK) polarized solution is a very important energymixture, which is widely used in the treating of ischemic heart disease.Whether GIK could be used in the healing of liver damage and acute hepatic failure, remains need us to explore.【Objectives】1. To investigate the changes of serum levels of IL-4,IL-6,and IL-10 in HBV-infected patients with hepatic disease,2. To study the relationship between COX-2 catalysates which are associated with cytokines with serious hepatitis,3. To explore the possible application of High-dose Glucose-insulin -potassium in the therapy of acute-hepatic-failure.【Methods】Serum samples from a total 57 HBV-infected patients with well-characterized clinical profiles and 25 healthy controls were assessed by ELISA. Samples from a total 50 serious hepatitis patients with well-characterized clinical profiles and 25 general HBV-infected patients were assessed by ELISA,3. High-dose GIK could effectively reverse acute hepatic failure through affecting the Th2 subgroup cytokines. In the control study of treatment, traditional protection ways of liver were taken, and high-dose GIK was used in treatment group, which iv drop with 500ml 25% glucose parenteral solution, 25u insulin and 1.5g KCL each 12h for 15 days. And samples befor and after treatment were collected.【Results】1. IL-4 and IL-6, produced by Th2 cell, were closely correlated withthe HBV-infected liver diseasesCompared with the healthy control group, serum IL-4 and IL-6 were uniformly elevated in all HBV-infected patients (HBV-infected patients vs. healthy control IL-4 t=3.19, P=0.002;HBV-infected patients vs. healthy control IL-6 t=3.26, P=0.002). But there were no significant difference of these cytokines levels among the different types of patients. However, serum IL-10 levels, was low in both and showed no association with clinical presentation.2. COX-2 catalysates which are associated with cytokines were correlated with the progression of serious hepatitisCompared with the general HBV-infected patients, serum TXB2 and 6ketoPGF1αlevel were uniformly elevated in all serious hepatitis patients (acute serious hepatitis patients vs. general HBV-infected patients t=4.79,P<0.005;sub-acute serious hepatitis patients vs. general HBV-infected patients t=4.53,P<0.002;chronic serious hepatitis patients vs. general HBV-infected patients t=4.39,P<0.001). But there were no significant difference of these cytokines levels among the different types of serious hepatitis patients.3. Application of High-dose Glucose-insulin-potassium in the therapy of Acute-hepatic-failureCompared with the control therapy group, high-dose Glucose- insulin-potassium could significantly improve the liver function, reduce the inflammation, apoptosis and necrosis of the liver. In a word, high-dose Glucose-insulin-potassium could effectively protect the liver cells. The mechanism may be the high-dose Glucose-insulin-potassium could inhibit the generation of IL-1, 4,6, TNF and promote the production of IL-10.【Conclusion】1.Serum IL-4,IL-6 but not IL-10 were associated with the clinical presentation in HBV-infected patients.2. COX-2 metabolism products, TXB2 and 6-keto-PGF1α, were associated with the clinical progression of serious hepatitis, especially T/6-K ratio was an effective biological marker for prognosis and diagnosis for serious hepatitis.3. Flushing dose GIK could significantly reverse the acute hepatic failure, which might be associated with the cytokines.