锌对人白细胞介素2产量的影响

锌是人体必需的营养元素,对机体的免疫功能也有重要作用,几乎所有的免疫应答的正常进行都依赖于适当的含锌量。锌不足可以降低抗体形成,减少细胞介导的细胞毒活性、NK 活性及巨噬细胞的吞噬作用和胞内杀伤力,临床表现为对传染的易感性增高。伴随衰老过程出现的免疫功能低下,也可能与锌代谢的改变有关。

5类茶叶对正常和血虚小鼠脾淋巴细胞产生白细胞间素－2的影响

观察了乌龙茶、茉莉花茶、绿茶、红茶和白茶对正常和血虚小鼠脾淋肥细胞产生白细胞间素－２（ＩＬ－２）的影响。结果表明，５类茶均能显著促进正常小鼠脾淋巴细胞产生ＩＬ－２，显著促进正常小鼠混合脾淋巴细胞产生ＩＬ－２，显著提升血虚小鼠脾淋细胞分泌ＩＬ－２的水平；红茶、白茶能显著提升血虚小鼠混合脾淋巴细胞分泌ＩＬ－２水平，而乌龙茶、花茶和绿茶的作用则不明显．

白细胞间素—2冻干制品的活性检测

试制三批大鼠白细胞间素-2(IL-2)粗制品,每批均同时制成冷冻制品及冻干制品,分别保存于-30℃和4℃冰箱。经过2.5年连续同步检测,并进行样品IL-2生物活性的稳定性比较。结果表明.冷冻制品与冻干制品存放不同时间其生物活性差异无显著意义(P>0.05),且冻干制品具有更多的优点。

表达谷胱甘肽S转移酶-蜂毒素-^(88)精氨酸变体白细胞介素2工程菌的发酵条件研究

目的研究重组蜂毒素-88精氨酸变体白细胞介素2(Melittin-88ArgIL-2)工程菌的发酵条件。方法采用摇瓶发酵,对含pGEX-4T-2-Melittin-88ArgIL-2重组质粒的工程菌进行诱导表达,研究诱导温度、诱导时间、诱导剂浓度、培养基的pH值等对谷胱甘肽S转移酶-Melittin-88ArgIL-2表达量的影响。同时研究培养温度对产物表达形式的影响。结果根据优化的条件,蛋白质的表达量占菌体总蛋白质的36%左右。结论确立了该重组melittin-88ArgIL-2工程菌的发酵条件。

ILF2及NF90在口腔鳞状细胞癌中的表达及临床意义

目的探讨白细胞介素增强结合因子2(Interleukin enhancer-binding factor 2,ILF2)及核因子90(Nuclear factor 90,NF90)在口腔鳞状细胞癌(Oral squamous cell carcinoma,OSCC)中的表达及临床意义。方法使用免疫组织化学(Immunohistochemistry,IHC)及实时荧光定量检测(Quantitative real-time PCR,qRT-PCR)方法检测ILF2及NF90在OSCC和正常口腔黏膜(Normal oral mocusa,NOM)组织中的表达水平,并进一步分析二者表达情况与OSCC患者临床病理特征以及预后之间的关系;使用Oncomine及GEPIA数据库分析二者在不同组织中的表达情况。结果与NOM组织对比,ILF2及NF90在OSCC组织中高表达(P<0.05),二者在OSCC组织中的表达具有相关性(φ=0.540,P<0.001);Oncomine数据库结果显示ILF2及NF90同样在OSCC组织中高表达(P<0.05);GEPIA数据库结果显示ILF2及NF90在OSCC中的表达呈正相关(r=0.600,P<0.001)。ILF2及NF90的表达情况与OSCC的肿瘤分化程度、TNM分期及淋巴结是否转移相关(P<0.05);生存分析显示ILF2和NF90高表达的患者总生存期较短,且ILF2及NF90因子的高表达和肿瘤分化程度是影响患者总生存期的独立危险因素(P<0.05)。结论ILF2和NF90在OSCC中高表达,且两者具有相关性,对OSCC患者的预后有不良影响,提示二者可以作为OSCC发生发展新的诊断标志物及预后评估指标。

二青汤对系统性红斑狼疮血清SIL—2R的疗效观察

系统性红斑狼疮（ＳＬＥ）是一种累及多系统器官的自身免疫性疾病。近年来，可溶性白细胞α受体（ＳＩＬ－２Ｒ）已成为ＳＬＥ临床研究中较为活跃的项目，ＳＩＬ－２Ｒ测值与ＳＬＥ患者血清学指标改变及疾病活动性具有相关性，ＳＩＬ－２Ｒ浓度变化与临床病情控制相一致，...

Th细胞因子变化与妊娠高血压综合征关系的探讨

目的探讨妊高征孕妇与正常孕妇细胞因子变化以及在发病机制中的作用。方法住院分娩的孕妇80例,其中妊高征50例(轻度19例、中度15例、重度16例),正常足月妊娠30例(对照组)。采集静脉血2ml,酶联免疫吸附试验检测血清中IL-2、IL-6、TNF-α浓度。结果TNF-α对照组浓度低于轻、中、重度妊高征组(P<0.05),IL-2对照组浓度低于中、重度妊高征组(P<0.05)。IL-6对照组浓度低于重度组(P<0.05);TNF-α/IL-6,IL-2/IL-6对照组与轻、中、重度妊高征组之间的差异无统计学意义(P>0.05)。妊高征患者TNF-α、IL-2、IL-6之间呈正相关性。结论妊高征孕妇体内细胞因子TNF-α、IL-2、IL-6浓度较正常孕妇体内升高,妊高征的发病与机体异常的机体异常的免疫激活,炎症状态有关有关。

Assessment of natural and interleukin-2-induced production of interferon-gamma in patients with liver diseases

AIMS To clarify whether the lower interferon gamma (IFNγ) production by lymphocytes in patients with liver diseases is due to defects of lymphocytes themselves or of other cofactors such as interleukin-2(IL-2). METHODS Peripheral blood mononuclear cells (PBMCs) from patients with various liver diseases were cultured with or without PHA and IL-2. The cells were harvested and counted and the su- pernatants were tested for IFNγ by a sensitive and quantitative ABC-ELISA. RESULTS IFNγ was not round in serum samples from patients as well as normal individuals. However,in supernatants of non-in- duced and induced PBMCs,IFN7 was detected by ABC-ELISA. In non-induced PBMCs (group 1),the content of IFNγ in super- natants from control,CAH,CPH and HCC was 8.72 μg/L, 5.03 μg/L,6.02 μg/L and 4.91 μg/L respectively. The pro- duction of IFNγ in liver disease was significantly decreased,com- pared to control. In group 2 in which PBMCs were stimulated with PHA,the content of IFNγ was 22.71,17.12,14.54 and 17.63 μg/L respectively. In group 3 in which PBMCs were in- duced by IL-2,the amount of IFN7 in supernatant from control (60.67 μg/L) was much larger than those from CAH (21.70 μg/ L),CPH (24.00 μg/L) and HCC (19.15 μg/L) (P<0.01). Comparing the amount of IFNγ in group 3 (IL-2-induced) with that in group 1 (non-induced),we found that IFNγ production was en- hanced by nearly 4 folds in liver diseases and by over 7 folds in control,Whereas the number of PBMCs,whether from liver dis- eases or from control,was increased by only approximately 3 folds. CONCLUSIONS The decreased production of IFNγ in liver dis- eases including HCC is mainly due to endogenous defects of lym- phocytes though the defects of stimulating cofactors such as IL-2 may also be involved.

Determination of IL-2/IL-2R system in patients with liver cirrhosis.and carcinoma

AIMS To.determine the interleuking-2 and interleukin- 2 receptor (IL-2/IL-2R) system in patients with liver cirrhosis and carcinoma and compare their immune functions. The clinical significance is also discussed. METHODS Fifty patients with Liver cirrhosis (LC), 50 patients with hepatocellular carcinoma (HCC) and 30 normal controls were studied. The expression of mlL-2R was examined by immunofluorescence. IL-2's activity and serum level of soluble interleukin-2 recep- tor (sIL-2R) were measured by enzyme linked im- munosorbent assay. RESULTS IL-2's activity and the percentage of mIL- 2R expression in carcinoma were significantly lower than those in cirrhosis (P<0.01) and controls (P< 0.01),while the IL-2's activity and the expression of mlL-2R in cirrhosis were also lower than normal controls (P<0.05). The serum level of sIL-2R in carcinoma was significantly higher than that in cirrhosis (P<0.05) and controls (P<0.01),and the level in cirrhosis was higher than in controls (P<0.05). CONCLUSIONS Patients with liver cirhosis and car- cinoma share the decreased immune function of similar nature,but the latter has a more profound degree. Such resemblance in immune disturbances may be the important factor affecting the carcinogenesis of cirrhotic liver.

白血病患者IL-2活性水平的定量分析

采用依赖白细胞介导素2(IL-2)的 CTLL-2建株细胞作为检测系统,用人重组 IL-2作对照(参照 NCI 所定的 u/ml),对15例白血病初发期患者、6例缓解期患者和26例正常人的外周血单个核细胞用 PHA-M 刺激,定量测定其 IL-2产量。结果表明:(1)正常人群中 IL-2活性水平为359.6±37.7u/ml;(2)白血病初发期患者 IL-2活性水平为251.5±184u/ml,其中11例低于或接近正常水平,占73%;(3)白血病缓解期患者 IL-2活性水平高于正常人群和初发期患者,为521±316u/ml。以上结果对研究白血病患者的免疫状态和选用适当的治疗方案有实际意义。

Serum Levels of Interleukin-2 and -10 in Patients with Early Syphilis

Objective: To investigate the roles of interleukin-2(IL-2) and interleukin-10 (IL-10) in pathogenesis ofearly syphilis. Methods: The serum levels of IL-2 and IL-10 in 48patients with early syphilis were detected by ABC-ELISA. Results: (1) The level of IL-2 in the patients withearly syphilis was significantly higher than that inhealthy controls, while that of IL-10 was lower(P<0.001 and P<0.001). (2) The levels of IL-2 and IL-10 were almost identical in patients with primary andsecondary syphilis (P>0.05), as well as between dif-ferent RPR titers (P>0.05). (3) After therapy, the levelof IL-2 decreased markedly (P<0.05), while that of IL-10 increase (p>0.05). (4) A significant correlation wasfound between the serum levels of IL-2 and IL-10 (r=0.5385 P<0.05). Conclusions: Th1 up-regulation occurs in patientswith early syphilis, and plays an active role in fightingagainst TP infection.

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.

Interleukin-2 gene-encoded stromal cells inhibit the growth of metastatic cholangiocarcinomas

AIM： To demonstrate bone marrow stromal cells （BMSCs） can be used as an attractive target for genetic modification in the treatment of malignant diseases. METHODS： Using a hamster model of biliary cancer, we investigated the therapeutic effects of interleukin-2 （IL-2） gene-modified BHSCs. Syrian golden hamsters were injected via the femoral vein with 5×10^5 cells of the KIGB-5 biliary cancer cell line （n=20）. One week later, the hamsters were injected intraperitoneally with BMSCs containing Ad/hIL-2 and Ad/△E1, unmodified BHSCs, or RPHI only （control） and observed for 12 wk （n=5/each group）. RESULTS： All hamsters treated with BMSCs containing Ad/hIL-2 survived with no evidence of the disease during this period. In contrast, hamsters in the other three groups showed disseminated metastases involving the lungs as eady as 4 wk.CONCLUSION： Ad/IL-2 therapy is effective in the treatment of biliary cancer.

Immunologic changes to autologous transfusion after operational trauma in malignant tumor patients:Neopterin and Interleukin-2

Objective:To estimate the impact of autologous transfusion on the status of perioperative immune activation inmalignant tumor patients.The Serum Neopterin and Interleukin-2(IL-2)were measured.Methods:Sixty patients undergoingelective radical resection for malignant stomach tumor were enrolled in the prospective study and assigned to the following groups:(Ⅰ)Group A received autologous transfusion;(2)Group H received allogeneic transfusion.The perioperative course(Beforeinduction of anesthesia,after operation and 5 d after operation)of Neopterin and IL-2 was compared.Results:In group A,SerumNeopterin was significantly lower than baseline alter operation and IL-2 had no significant changes.In group H,both SerumNeopterin and IL-2 were significantly lower than baseline alter operation and 5 d after operation.Compared with group A,SerumNeopterin was significantly lower than baseline alter operation and 5 d after operation and IL-2 was significantly lower thanbaseline 5 d alter operation.Conchision:Autologous transfusion decreased the perioperative immune suppression in malignantstomach tumor patients.

Effects of Warm Needling at Zusanli(ST 36)on NO and IL-2 Levels in the Middle-Aged and Old People

42 middle-aged and old people at the age between 55-70 years were selected and given the warm needling at Zusanli (ST 36), and their IL-2 and NO contents of peripheral blood before and after acupuncture were determined. The results showed that IL-2 and NO contents increased significantly after the warm needling (P<0.01).

mIL-2R,T cell subsets & hepatitis C

AIM: To study the levels of membrane interleukin-2 receptor (mIL-2R) and T cell subsets in peripheral blood mononuclear cells (PBMC) from patients with hepatitis C and their role in the pathogenesis of hepatitis C. METHODS: The levels of mIL-2R and T cells subsets in PBMC were detected by biotin- streptatividin (BSA) technique before and after stimulation with PHA in 203 patients with hepatitis C with HCV-RNA(+), anti-HCV(+), anti-HCV(-). RESULTS: The total expressive levels of mIL-2R before and after stimulation with PHA(0.03+/-0.01, 0.03+/-0.02, 0.04+/-0.02, 0.36+/-0.03), and T cell subsets in PBMC (0.62+/-0.06, 0.37+/-0.05, 0.35+/-0.07) were all lower in patients with hepatitis C than those in normal controls (0.66+/-0.07, 0.41+/-0.06, 0.31+/-0.05, P【0.01). Among the patients, the levels of mIL-2R were lower in silence than those in situation of PHA inducting (P【0.01). However, the levels of mIL-2R were similar in acute hepatitis C to that in chronic hepatitis C (P】0.05). The levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+) were lower and CD(8)(+) was higher in patients with acute and chronic hepatitis C with anti-HCV(+) than those in normal controls (0.62+/-0.06, 0.37+/-0.05, 0.35+/-0.07, 1.18+/-0.30, 0.61+/-0.07, 0.37+/-0.05, 1.39+/-0.33, 0.31+/-0.05, P【0.05-P【0.01). CONCLUSION: The cellular immunity is obviously changed in patients with hepatitis C. The levels of mIL-2R and activation of T cells are closely associated with chronicity of hepatitis C.

High efficient mammalian expression and secretion of a functional humanized single-chain Fv/human interleukin-2 molecules

AIM： To construct and produce a recombinant bispecific humanized single-chain Fv （sFv） /Interleukin-2 （IL-2） fusion protein by using mammalian cells. METHODS： The sFv/IL-2 protein was genetically engineered, and transfected to mammalian cells to determine whether the mammalian protein folding machinery can produce and secrete active sFv/IL-2 with high efficiency. RESULTS： The fusion protein was constructed and high efficiently expressed with yields up to 102 ±4.2 mg/L in culture supernatant of the stably transfected 293 cell line. This recombinant fusion protein consisted of humanized variable heavy （VH） and light （VL） domains of monoclonal antibody （mAb） 520C9 directed against the human HER-2/neu （c-erbB2） proto-oncogene product p185, and human IL-2 connected by polypeptide linker. The fusion protein was shown to retain the immunostimulatory activities of IL-2 as measured by IL- 2-dependent cell proliferation and cytotoxicity assays. In addition to its IL-2 activities, this fusion protein also possessed antigen-binding specificity against p185, as determined by indirect ELISA using p185 positive SKOV 3ip1 cells. CONCLUSION： The large-scale preparation of the recombinant humanized sFv antibody/IL-2 fusion protein is performed with 293 cells. The recombinant humanized sFv antibody/IL-2 fusion protein may provide an effective means.of targeting therapeutic doses of IL-2 to p185 positive tumors without increasing systemic toxicity or immunogenicity.

A Clinical observation of the therapy for malignant hydrothorax by intra-thoracic injection using IL-2 combining with Cisplatin

Objective: The aim of our study was to explore the short-term effects and complication of interleukin-2 (IL-2) combining with Cisplatin in the treatment of malignant hydrothorax.Methods: Sixty-two cases patients with malignant hydrothorax were randomly divided into two groups.Observation group was 31 examples,thoracic cavity injection IL-2 and Cisplatin;31 cases in control group using Cisplatin alone intra-thoracic injection.The regime of every week for 1–4 weeks was used to observe short term effects and complications.Results: The total response rate in observe group was higher than that in control group (90.3% vs.68.1%),which had statistically significant difference (P < 0.05).The complications included gastrointestinal tract reaction,bone marrow inhibition,chest pain and fever.The incidence rates of chest pain and fever in observe group was slightly higher than that in control group,but there was no statistically significant difference (P > 0.05).Conclusion: The IL-2 combining with Cisplatin intra-thoracic injection for malignant hydrothorax has the features of good therapeutic effects and slight poisonous side effects,which is worth to be used in clinic.

TREATMENT OF 23 PATIENTS WITH ADVANCED GASTRIC CANCER BY INTRAVENOUSLY TRANSFER OF AUTOLOGOUS TUMOR-INFILTRATING LYMPHOCYTES COMBINED WITH rIL-2

Tumor-infiltrating lymphocytes (TIL)isolated from metastatic lymph nodes in patients with nonoperable advanced gastric cancer were induced to become LAK-like cytotoxic activrty of TIL after in vitro culture with rlL-2.Twenty-three patients with advanced gastric cancer were treated by intravenously transfer of autologous TIL combined with rlL-2. The tumor forus disappeared (complete remission, CR) in 3 patients (13. 0%) and significantly decreased (partial remission, PR) in 5 patients (21. 7%). Fifteen patients did not respond to the treatment. The amount of soluable IL-2 receptor in serum was significantly decreased after treatment, the cytotoxicity of NK cells and OT test were significantly increased. No significant difference in CD4/CD8 was found between before and after treatment. No serious side effect was obseved in the treatment.

EFFECTS OF ACUMOXI ON IL2-IFN-NKC IMMUNOREGULATORY NETWORK AND ITS RELATED MACROPHAGE-IL1-Th NETWORK AND ON TUMOR——Observation on the Effect of Acumoxi on the Macrophage-IL1-Th Network and on the Metastasis of Hepatoma

Objective: To observe the effect of acumoxi (acupuncture and moxibustion) on macrophage (Mφ)-lL1-Th net-work and hydroperitoneum hepatoma (H 22) metastasis in mice. Methods: A total of 36 BALB/ c male mice bearing H 22 are randomly divided into control, acupuncture and acumoxi groups with 12 cases in each group. In the later 2 groups, Dazhui (GV 14) and Guanyuan (CV 4) are punctured once daily, continuously for 18 days, and in acumoxi group, the two acupoints were also moxibustioned alternatively with moxa stick once every day. After killing the mice, the tissue samples of the 3 groups are treated routinely step by step and analyzed by means of colorimetric analysis for determining the phagocytic function of the macrophages; and the content of IL1 of the Mφ supernatant is assayed with serum plate agglutination (SPA)-Ig floral hoop method of T helper cell (Th) monoclonal antibody; the weight of the reniportal lymph node, the kidney and the lung, and the number of the cancerous nodes on the pulmonary surface are calculated. Results: After acupuncture and moxibustion treatment, the immunoregulatory network indices of acumoxi group increase obviously compared with those of control group(P<0.01), showing an anti-metastasis effect of acumoxi on H 22. Conclusion: Results of the present study and those of our former research prove that acupuncture and moxibustion can suppress the tumor growth and H 22 metastasis by the enhancement of the immunoregulatory network.