OBJECTIVETo study the protective effect of atractylenolide I on immunological liver injury induced by BCG and LPS.

METHODKunming mice were randomly divided into 6 groups: the normal group, the model group, positive control biphenyl group, the atractylenolide I high does group, the atractylenolide I middle dose group and the atractylenolide I low dose group (60, 120, 240 mg x kg(-1)), with 12 mice in each group. Immunological liver injury in mice was induced by BCG and LPS to compared liver index and spleen index and detect content of serum ALT, AST, MDA and GSH-px in serum and NO, iNOS, TNF-alpha in serum and liver homogenate. Liver pathological changes were observed by HE staining.

RESULTBoth of atractylenolide I and biphenyl remarkably decrease the increased live index and spleen index (P < 0.05), improve the histopathological changes in liver and pathological grades of liver tissues and relieve the inflammatory reaction induced by BCG and LPS. They showed a notable effect in improving MDA and GSH-px in serum.

CONCLUSIONAtractylenolide I can obviously protect immunological injury liver a dose-dependent manner within the range of test doses. Its mechanism may be related to release or over expression of inhibitory inflammatory medium such as NO, iNOS and TNF-alpha.

Animals ; Chemical and Drug Induced Liver Injury ; immunology ; metabolism ; pathology ; prevention & control ; Lactones ; pharmacology ; Lipopolysaccharides ; adverse effects ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mice ; Mycobacterium bovis ; immunology ; Oxidative Stress ; drug effects ; immunology ; Sesquiterpenes ; pharmacology

OBJECTIVETo evaluate the effect of emodin on hepatocellular apoptosis following orthotopic liver transplantation (OLT) in rats.

METHODThe LEW --> BN OLT models were established. A total of 24 rats were divided randomly and equally into 4 groups. Group A was treated with normal saline at dose of 0.5 mL x d(-1) intraperitoneally from 1st day to 8 th day after operation. Group B, CsA at dose of 10.0 mg x kg(-1) x d(-1). Group C, emodin at dose of 50.0 mg x kg(-1) x d(-1). Group D, CsA at dose of 10.0 mg x kg(-1) x d(-1) and emodin at dose of 50.0 mg x kg(-1) x d(-1). Fifteen days after operation, rejection active index (RAI) and hepatocellular apoptosis index (AI) was confirmed after observing the pathologic change of transplanted liver in recipients.

RESULTRespectively, the RAI of group A, B, C, D was 7.67 +/- 0.98, 5.17 +/- 0.40, 5.83 +/- 0.75, 3.83 +/- 0.75 and the AI of group A, B, C, D was 35.83 +/- 2.320, 15.83 +/- 1.33, 16.50 +/- 2.35, 11.50 +/- 1.05. The RAI and AI of group B, C, D was significantly lower than group A (P < 0.01) and group D was significantly lower than group B, C too (P < 0.05). There was no significant distinction between group B and C in RAI and AI.

CONCLUSIONEmodin has the effect of reduce the hepatocellular apoptosis following OLT in rats and the effect can stronger by CsA.

Animals ; Apoptosis ; drug effects ; Emodin ; pharmacology ; Graft Rejection ; Hepatocytes ; cytology ; drug effects ; immunology ; Liver Transplantation ; Male ; Rats ; Rats, Inbred Lew

Antineoplastic Agents ; chemistry ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; pathology ; Cytokines ; immunology ; Drug Screening Assays, Antitumor ; Glypicans ; antagonists & inhibitors ; immunology ; Humans ; Ligands ; Liver Neoplasms ; drug therapy ; immunology ; pathology ; T-Lymphocytes ; drug effects ; immunology

OBJECTIVETo observe the therapeutic effects of beta-elemene combined DC/Dribble vaccine in treating mice with hepatic cancer, thus exploring their anti-tumor mechanisms.

METHODSDentritic cells were derived from Balb/c mice's spleen and their phenotypes were identified. Using hepatic cancer cell line BNL1MEA.7R.1 (abbreviated as BNL) originated from Balb/c mice as target cell, DC/Dribble vaccine was prepared via raising the antigen representing carrier autophagosomes (DRips in Blebs, DRibbles), which were rich in tumor antigen information. The mice previously immunized were divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The PBS was subcutaneously and intraperitoneally injected to mice in the control group. The beta-elemene was intraperitoneally injected at the daily dose of 50 mg/kg to mice in the beta-elemene group and the combined group for 7 successive days. DC/Dribble vaccine was injected into the lymph node of mice in the vaccine group and the combined group on the 1st day, and DC/Dribble vaccine was subcutaneously injected on the 3rd day and the 5th day. All the mice were sacrificed on the 10th day. Their spleens were obtained sterilely, and the suspension was incubated with or without Dribble. The cells were inoculated for 72 h. The contents of IFN-gamma in the supernatant were measured by ELISA. In addition, the spleen cells obtained from the combined group were incubated with different stimulations for 72 h, which were then divided into the control group, the DRibble group, the DC group, and the DC/Dribble vaccine group. The supernatant of cultured cells were collected and the contents of IFN-gamma were measured by ELISA. The liver tumor-bearing mouse model was established, and then the BNL bearing mice were randomly divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The treatment ways were the same as the immune ways. The tumor size and the survival period were observed in each group. On the 23rd day the mice were sacrificed. The tumor tissue was stripped and stained by HE staining. The pathomorphological manifestations of the tumor tissue were observed by light microscope.

RESULTSIn vitro detection of mice immunized previously by different ways showed that the secretion of IFN-gamma was significantly higher in the combined group than in the rest groups (P < 0.01). The secretion of IFN-gamma was significantly higher in the beta-elemene group and the vaccine group than in the control group (P < 0.01). The spleen cells could be stimulated to secrete a large amount of IFN-gamma in the vaccine group and the Dribble group (P < 0.01). When the beta-elemene was 10 microg/mL as the stimulating dose, the secretion of IFN-gamma obviously increased (P < 0.01). In vivo observation showed that the growth velocity of tumors in mice of the combined group was slowed down. There was statistical difference in the tumor area or the survival period of mice in the combined group, when compared with the other groups (P < 0.01). In HE staining, the surrounding connective tissues of the tumor were wrapped tightly and compactedly, with infiltration of a large amount of inflammatory cells.

CONCLUSIONSbeta-elemene combined DC/Dribble vaccine could induce specific immune cells to secrete secretory cells, thus exerting its anti-tumor effect. Its immunological effects might be associated with enhancing the DC antigen presenting function.

Animals ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Dendritic Cells ; drug effects ; immunology ; Female ; Liver Neoplasms ; drug therapy ; immunology ; Mice ; Mice, Inbred BALB C ; Sesquiterpenes ; pharmacology

BACKGROUNDThere has been increasing interest in the research into cytomegalovirus (CMV) pneumonia after liver transplantation (LT). This study was undertaken to investigate the immunomodulatory therapy of CMV pneumonia after LT.

METHODSSix patients with CMV pneumonia after LT from October 2003 to November 2005 were analyzed retrospectively. They were diagnosed according to clinical manifestations, chest X-ray findings and pathogenic changes and given comprehensive therapy including mainly immunomodulation therapy and anti-viral medication. At the early stage of CMV pneumonia, the dose of immunosuppressive agents was decreased or ceased, instead replaced by immunoenhancement therapy. During recovery period from CMV pneumonia, the dose of immunosuppressive agents was given again or enhanced, and immunoenhancement therapy was ceased. The liver function of the patients was monitored closely during the treatment.

RESULTSIn this series, five patients were survived and one died. The liver function of the six patients remained normal during the treatment, and no episode of acute rejection took place.

CONCLUSIONSPoor immunity is the pathogenic basis of CMV pneumonia after LT. At early stage of CMV pneumonia, the immunity of the patients should be enhanced, and during the recovery period from CMV pneumonia, immunosuppressants should be given again but immunoenhancement therapy ceased. Individualized immunomodulatory therapy is essential to the treatment of CMV pneumonia after LT.

Adjuvants, Immunologic ; therapeutic use ; Adult ; Cytomegalovirus Infections ; drug therapy ; immunology ; Humans ; Liver Transplantation ; adverse effects ; immunology ; Lymphocyte Activation ; Male ; Middle Aged ; Pneumonia, Viral ; drug therapy ; immunology

BACKGROUNDLymphocyte subsets play important roles in rejection in liver transplant recipients, and the effect of splenic function on these roles remains unknown. The aim of this study was to explore the feasibility to adjust immunosuppressive agents based on splenic function status through detecting the lymphocyte subsets in liver transplantBeijing recipients.

METHODSThe lymphocyte subsets of 49 liver transplant recipients were assessed in the 309th Hospital of Chinese People's Liberation Army between June 2014 and August 2015. The patients were divided into splenectomy group (n = 9), normal splenic function group (n = 24), and hypersplenism group (n = 16). The percentages and counts of CD4+ T, CD8+ T, natural killer (NK) cell, B-cell, regulatory B-cell (Breg), and regulatory T-cell (Treg) were detected by flow cytometer. In addition, the immunosuppressive agents, histories of rejection and infection, and postoperative time of the patients were compared among the three groups.

RESULTSThere was no significant difference of clinical characteristics among the three groups. The percentage of CD19+CD24+CD38+ Breg was significantly higher in hypersplenism group than normal splenic function group and splenectomy group (3.29 ± 0.97% vs. 2.12 ± 1.08% and 1.90 ± 0.99%, P = 0.001). The same result was found in CD4+CD25+FoxP3+ Treg percentage (0.97 ± 0.39% vs. 0.54 ± 0.31% and 0.56 ± 0.28%, P = 0.001). The counts of CD8+ T-cell, CD4+ T-cell, and NK cell were significantly lower in hypersplenism group than normal splenic function group (254.25 ± 149.08 vs. 476.96 ± 225.52, P= 0.002; 301.69 ± 154.39 vs. 532.50 ± 194.42, P= 0.000; and 88.56 ± 63.15 vs. 188.33 ± 134.51, P = 0.048). Moreover, the counts of CD4+ T-cell and NK cell were significantly lower in hypersplenism group than splenectomy group (301.69 ± 154.39 vs. 491.89 ± 132.31, P= 0.033; and 88.56 ± 63.15 vs. 226.00 ± 168.85, P = 0.032).

CONCLUSIONSplenic function status might affect the immunity of liver transplant recipients, that should be considered when we make immunosuppressive protocols.

CD4-Positive T-Lymphocytes ; drug effects ; immunology ; Female ; Humans ; Hypersplenism ; immunology ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Killer Cells, Natural ; drug effects ; immunology ; Liver Transplantation ; methods ; Lymphocyte Subsets ; drug effects ; immunology ; Male ; Middle Aged ; Retrospective Studies ; Sirolimus ; administration & dosage ; therapeutic use ; Spleen ; drug effects ; immunology ; T-Lymphocytes, Regulatory ; drug effects ; immunology

Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.
Animals ; Chemical and Drug Induced Liver Injury ; etiology ; immunology ; Chemokine CCL2 ; genetics ; immunology ; Diterpenes ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Epoxy Compounds ; adverse effects ; Female ; Humans ; Interleukin-6 ; genetics ; immunology ; Intracellular Signaling Peptides and Proteins ; genetics ; immunology ; Liver ; drug effects ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; immunology ; Phenanthrenes ; adverse effects ; Tripterygium ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVETo investigate the effects of Compound Glycyrrhizin Injection (CGI) on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment (IM-LI) and to explore its clinical therapeutic effect.

METHODSForty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group. All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up.

RESULTSBaseline of the percentage of CD3 + , CD8 + lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD4 + lymphocyte and the CD4 + /CD8 + ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children ( P<0.01). These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group (P<0.01).

CONCLUSIONCellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

Child ; Child, Preschool ; Female ; Glycyrrhizic Acid ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Immunity, Cellular ; drug effects ; Infant ; Infectious Mononucleosis ; complications ; drug therapy ; immunology ; physiopathology ; Injections ; Liver ; drug effects ; physiopathology ; Liver Diseases ; drug therapy ; Male ; T-Lymphocyte Subsets ; drug effects

OBJECTIVETo investigate the clinical significance of liver function and autoantibodies in patients with acute or chronic drug-induced liver injury.

METHODS51 patients with drug-induced liver injury were divided into acute drug induced liver injury group and chronic drug induced liver injury group, liver function and autoantibodies were compared between these two groups.

RESULTSThere was no significant difference (P more than 0.05) in alanine aminotransferase [(412.1+/-387.5) U/L and (376.0+/-319.7) U/L], aspartate aminotransferase [(352.5+/-457.9) U/L and (198.8+/-142.7) U/L], total bilirubin [(109.7+/-104.80)micromol/L and(102.4+/-135.7)micromol/L], direct bilirubin [(66.4+/-73.3)micromol/L and (61.2+/-72.1)micromol/L], alkaline phosphatase [(133.4+/-50.1) U/L and (147.4+/-97.3) U/L], gamma-glutamyltransferase [(139.9+/-134.1) U/L and (180.6+/-227.9) U/L], and albumin [(41.3+/-4.9) g/L and (39.8+/-5.3)g/L] between these two groups, however, the level of globulin [(25.1+/-5.3) g/L and (28.6+/-5.1) g/L] was significantly different between these two groups (P less than 0.05). The titers of Anti-nuclear antibody (ANA) and smooth muscle antibody (SMA) were less than or equal to 1:320 in patients with acute drug induced liver injury. The titers of ANA, antimitochondrial antibody (AMA), and SMA were more than or equal to 1:320 in most of the patients with chronic drug induced liver injury.

CONCLUSIONLiver function has no value in the diagnosis of acute or chronic drug induced liver injury. High titer autoantibodies are found in patients with chronic drug induced liver injury.

Acute Disease ; Adult ; Antibodies, Antinuclear ; blood ; Autoantibodies ; blood ; Chemical and Drug Induced Liver Injury ; blood ; diagnosis ; immunology ; Diagnosis, Differential ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Liver ; pathology ; physiopathology ; Liver Function Tests ; Male ; Microsomes ; immunology ; Middle Aged ; Muscle, Smooth ; immunology

OBJECTIVE: To investigate the antitumor activity of decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model. METHODS: Hepatoma H22 tumor-bearing mouse models were randomized into model group, cyclophosphamide (CTX) group, and low-, moderate-, and high-dose decoction groups (JW-L, JW-M, and JW-H groups, respectively). The antitumor activity of decoction was assessed by calculating the tumor inhibition rate and pathological observation of the tumor tissues. Immunohistochemistry was used to detect the expressions of Bax, Bcl-2, Bax/Bcl-2 and caspase-3 in the tumors. The liver and kidney toxicity of decoction was analyzed by evaluating the biochemical indicators of liver and kidney functions. The immune function of the tumor-bearing mice were assessed by calculating the immune organ index, testing peripheral blood routines, and detection of serum IL-2 and TNF-α levels using enzyme-linked immunosorbent assay. RESULTS: Compared with that in the model group, the tumor mass in CTX, JW-M and JW-H groups were all significantly reduced ( < 0.05) with cell rupture and necrosis in the tumors. Immunohistochemistry revealed obviously up-regulated expressions of Bax and caspase-3 and down- regulated expression of Bcl-2 protein with an increased Bax/Bcl-2 ratio in CTX, JW-M and JW-H groups. Treatment with decoction significantly reduced Cr, BUN, AST and ALT levels, improved the immune organ index, increased peripheral blood leukocytes, erythrocytes and hemoglobin levels, and up-regulated the levels of TNF-α and IL-2 in the tumor-bearing mice. These changes were especially significant in JW-H group when compared with the parameters in the model group ( < 0.01). CONCLUSIONS decoction has a strong anti-tumor activity and can improve the liver and kidney functions of tumor-bearing mice. Its anti-tumor effect may be attributed to the up-regulation of Bax, caspase-3, TNF-α and IL-2 levels and the down-regulation of Bcl-2 expression as well as the enhancement of the non-specific immune function.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; Liver ; drug effects ; pathology ; Liver Neoplasms ; drug therapy ; immunology ; metabolism ; pathology ; Mice ; Necrosis ; Neoplasm Proteins ; metabolism ; Random Allocation ; Up-Regulation