急性脑梗死患者脑脊液肿瘤坏死因子、白细胞介素6和8的变化

为探讨脑梗死患者脑脊液中肿瘤坏死因子、白细胞介素6、白细胞介素8水平的动态变化，采用酶联免疫吸附法分别测定30例脑梗死患者病期＜1周与病期＞4周以及20例健康老年人的脑脊液中肿瘤坏死因子、白细胞介素6、白细胞介素8水平。结果发现，脑梗死患者脑脊液肿瘤坏死因子、白细胞介素8水平较正常对照组增高、病期＜1周者脑脊液肿瘤坏死因子、白细胞介素8水平较病期＞4周者显著升高；病期＞4周者相比无明显改变（P＞0．05），但均高于正常对照组，而且神经功能缺损程度与脑脊液肿瘤坏死因子、白细胞介素8的含量呈明显正相关关系。结果提示，脑脊液肿瘤坏死因子、白细胞介素6、白细胞介素8水平的动态监测对脑梗死发生、发展及预后判断具有一定预测价值。     

Modulation of multidrug resistance by andrographolid in a HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line

OBJECTIVE To develop an HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line and to elucidate the effect of Andrographolid (AG), an extract from Andrographis paniculate, a medicinal herb on the HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line. METHODS An HCT‐8 colorectal cancer cell line was used and a high concentration of 5‐Fluorouracid (5‐FU) was introduced at the beginning to induce drug resistance, then the concentration of 5‐FU was increased in gradients. Approximately 7 months later, the cells grew stably in 2.0 µg/mL of 5‐FU, and the cell line was named HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line. The resistant index of HCT‐8/5‐FU cells to 5‐FU, adriamycin (ADM), cisplatin (DDP) was checked by MTT test, and a growth curve was drawn. The morphological changes were observed by both light and electron microscope. The function of P‐170 was detected by rhodamine staining. After the application of AG and co‐administration of 5‐FU, ADM and DDP, the growth curves and inhibition rate as well as apoptosis rate of HCT‐8/5‐FU at different concentrations of AG were evaluated by MTT and flow cytometry. Rhodamine staining was used to investigate the possible mechanism involved by AG. RESULTS The resistance index of HCT‐8/5‐FU to 5‐FU was 16.6, and a cross‐resistance to ADM and DDP was noticed. Compared with parental cells, HCT‐8/5‐FU cell's growth rate did not change significantly but the cell's morphology was remarkably changed as compared with parental cells. Overexpression of P‐170 by HCT‐8/5‐FU cell was indicated through rhodamine staining. AG at a low concentration showed weak inhibitory effect on HCT‐8/5‐FU. However, a remarkable inhibitory and apoptosis rate was shown when AG was co‐administered with 5‐FU, ADM and DDP, respectively. Interestingly AG alone could not induce apoptosis and change the cell cycles. AG might affect the expression of P‐170, which was indicated by rhodamine staining. CONCLUSIONS The HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line has been successfully developed and because it has cross‐resistance to 5‐FU, ADM and DDP, it might serve as an ideal multidrug resistance (MDR) model for colorectal cancer research. The mechanism of HCT‐8/5‐FU resistance to chemotherapeutic agents might be related to the overexpression of P‐170. Low concentrations of AG alone have no significant inhibition on HCT‐8/5‐FU and fail to induce apoptosis and to change cell cycles. AG might act as a chemosensitizer when co‐administered with 5‐FU, ADM and DDP, and the mechanism of reversal modulation of multidrug resistance by AG in the HCT‐8/5‐FU resistant cell line might be related to its downregulation of overexpression of P‐170.     

白细胞介素-1β和白细胞介素-6对妊娠相关血浆蛋白-A表达的影响

目的探讨炎性因子白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)对人冠状动脉平滑肌细胞(human coronary artery smooth muscle cell,HCASMC)表达妊娠相关血浆蛋白-A(pregnancy-associated plasma pro-tein-A,PAPP-A)的影响。方法应用20μg/L的IL-1β、10μg/L的IL-6各自刺激HCASMC,共同培养0、2、4、8、243、6 h后收集细胞。应用不同浓度的IL-1β(0、5、20、40μg/L)I、L-6(0、5、10、50μg/L)刺激HCASMC,共同培养6 h后收集细胞。应用实时定量聚合酶链反应的方法检测细胞内PAPP-A基因的表达量。结果在同剂量IL-1βI、L-6刺激下,PAPP-A的表达量在2 h时就开始发生上调,8 h达高峰,而后开始下降;在不同剂量IL-1βI、L-6刺激下,PAPP-A的表达量在实验剂量范围内随着剂量的加大呈上升趋势(IL-1β:r=0.972,P=0.000;IL-6:r=0.941,P=0.000)。结论炎性因子IL-1βI、L-6能促进HCASMC中斑块稳定相关标记物PAPP-A的表达,可能是炎症在急性冠状动脉综合征发生发展中的重要作用机制之一。     

P8 expression is induced in acinar cells during chronic pancreatitis

The p8 gene is barely expressed in the normal pancreas, but is overexpressed in acute pancreatitis. To elucidate the dynamic expression of p8 mRNA and its significance in the course of chronic pancreatitis, we investigated the p8 expression in spontaneous chronic pancreatitis in the WBN/Kob rat as well as in humans and arginine-treated rat pancreatic acinar AR4-2J cells. p8 mRNA was significantly increased at 12 weeks when chronic pancreatitis first appeared in the WBN/Kob rats. p8 was immunolocalized in the acinar cell nuclei. Acinar cell apoptosis was significantly increased at 12 and 20 weeks in the WBN/Kob rats. In AR4-2J cells, p8 mRNA was significantly induced at 4 hr after arginine addition. Apoptosis of AR4-2J cells was not increased during the strong expression of p8 mRNA. These results suggest that p8 is induced in the acinar cells during chronic pancreatitis as the self-defence mechanism against proapoptotic insults.     

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

BACKGROUND /AIMS: Interleukin-10 (IL-10) has been ascribed pro-viral but anti-fibrotic properties in chronic hepatitis C virus (HCV) infection. In this study, we examined the role of HCV-specific T-cell IL-10 response in patients with acute and chronic HCV infection. METHODS: Peripheral HCV-specific T-cell IL-10 and IFNgamma responses were measured in cytokine Elispot assay using overlapping HCV-derived peptides in patients with chronic (n=61), resolved (n=15) and acute (n=8) hepatitis C, looking for their onset, quantity, breadth and durability relative to clinical and virological outcomes. The source and effect of HCV-specific IL-10 response were determined in depletion and IL-10 neutralization experiments. RESULTS: Both HCV-specific IL-10 and IFNgamma responses were detected early within 1-2 months of acute clinical hepatitis C. However, only HCV-specific IL-10 response correlated with elevated liver enzymes, increased viremia and suppressed HCV-specific CD4(+) T-cell proliferation in acute infection. While these associations were lost in established chronic infection, HCV-specific IL-10 responses were increased in patients without cirrhosis while IL-10 blockade enhanced antiviral effector IFNgamma responses. CONCLUSIONS: HCV-specific IL-10 Tr1 responses may play a dual role in HCV infection, dampening effector T-cells to promote viral persistence in acute infection but also protecting against progressive fibrosis in chronic infection.     

Biological Interactions of Aging and Anemia: A Focus on Cytokines

Anemia is one of the characteristics of the frailty phenotype and is often observed in elderly patients. Although anemia in people of advancing age can often be attributed to underlying etiologies such as iron deficiency or chronic disease, some cases do not have any identifiable cause. Therefore, it has been suggested that the aging process itself might be an intrinsic factor in the development of anemia, possibly through the age-related dysregulation of certain proinflammatory cytokines such as interleukin-6 (IL-6). Although the mechanism underlying the association between increased IL-6 and anemia has not been fully elucidated, it has been suggested that, like with other cytokines, it involves direct inhibition of erythropoietin production or interaction with the erythropoietin receptor.     

Adult patients with t(8;21) acute myeloid leukemia had no superior treatment outcome to those without t(8;21): a single institution’s experience

Clinical features and treatment outcome of 31 patients over 16 years of age with t(8;21) acute myeloid leukemia (AML) were compared with 60 patients without t(8;21). Among 31 patients with t(8;21), 15 patients were classified as AML-M2 and 11 and 5 patients as AML-M4 and M1, respectively. Of these patients, 28 patients (90.3%) achieved complete remission and 22 patients received consolidative treatment: intermediate-dose cytarabine (IDAC) 11, high-dose cytarabine (HDAC) 6, and allogeneic bone marrow transplantation (BMT) 5. When compared with patients without t(8;21), we could not demonstrate better treatment outcome for t(8;21) AML [median event-free survival (EFS) and overall survival (OS) 10.3 and 12.5 months in AML with t(8;21) vs 11.5 and 15.6 months in AML without t(8;21)]. In the t(8;21) AML group, patients who received HDAC consolidation did not show superior treatment outcome to those who received other consolidative treatment [median EFS: IDAC 11.9 months vs HDAC 9.2 months vs allogeneic BMT 38.1 months (P=NS) and median OS: IDAC 17.8 months vs HDAC 12.0 months vs allogeneic BMT 47.3 months (P=NS)]. Similar treatment outcome between patients with and without t(8;21) and non-superior treatment outcome of HDAC consolidative chemotherapy in the t(8;21) AML group in our study is contradictory to previous reports.These two authors equally contributed to this study: K.-W. Lee and I. S. ChoiSupported by a grant CRI-01-07 from the Cancer Research Institute, Seoul National University College of Medicine, and a grant 05-2001-002 from the S.N.U.H. Research Fund     

Glycyrrhizin enhances interleukin-10 production by liver dendritic cells in mice with hepatitis

Background Glycyrrhizin (GL), an aqueous extract of licorice root, is known to have various immune-modulating and biological response-modifier activities. GL is used in patients with hepatitis to reduce the activity of liver inflammation; however, the mechanism underlying the anti-inflammatory activity of GL is poorly understood. As antigen-presenting dendritic cells (DC) in the tissue play a major role in the regulation of the inflammatory mucosal milieu during tissue inflammation, we studied whether the function of liver DC was altered by GL therapy in a murine model of concanavalin-A (Con A)-induced hepatitis.Methods Liver DC were propagated from control mice or mice with Con-A-induced hepatitis, and the effect of GL on liver DC was evaluated in vivo and in vitro.Results The levels of interleukin (IL)-10 produced by liver DC were significantly lower in mice with Con-A-induced hepatitis compared with control mice. However, treatment with GL caused increased production of IL-10 in mice with Con A-induced hepatitis. The increased production of IL-10 by mice with Con A-induced hepatitis was also confirmed in vitro by culturing liver DC with GL.Conclusions This study indicates that increased production of IL-10 by liver DC due to GL administration may be involved in downregulation of the levels of liver inflammation in mice with Con A-induced hepatitis.