目的探讨血清中细胞因子6(IL-6)、细胞因子10(IL-10)和高敏C反应蛋白(Hs-CRP)在小儿肺炎支原体肺炎(MPP)发病中的作用及临床意义。方法采用酶联免疫吸附法(ELISA)检测MPP患儿入院时和抗炎治疗后血清中IL-6、IL-10含量。用速率散射比浊...目的探讨血清中细胞因子6(IL-6)、细胞因子10(IL-10)和高敏C反应蛋白(Hs-CRP)在小儿肺炎支原体肺炎(MPP)发病中的作用及临床意义。方法采用酶联免疫吸附法(ELISA)检测MPP患儿入院时和抗炎治疗后血清中IL-6、IL-10含量。用速率散射比浊法测定Hs-CRP含量并与对照组间比较,并进行统计学分析。结果 MPP组治疗前IL-6为(19.15±1.34)pg/ml,IL-10(18.25±1.41)pg/ml,Hs-CRP(28.4±3.05)mg/L与对照组IL-6(6.32±0.57)pg/ml,IL-10(6.11±2.03)pg/ml,Hs-CRP(6.41±1.15)mg/L浓度比较差异有统计学意义(t=64.001、t=32.618、t=49.272、P<0.01);MPP组治疗第7~10 d IL-6(6.65±1.05)pg/ml,IL-10(6.89±1.66)pg/ml,Hs-CRP(6.86±1.24)mg/L浓度比对照组有所升高,但其差异无统计学意义。结论MPP患儿入院治疗前,治疗后血清IL-6、IL-10,Hs-CRP含量的变化对疾病的进展和疗效有一定指导意义,提示IL-6、IL-10和Hs-CRP在MPP发病机制中起重要作用。展开更多
AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METH...AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS: Male Sprague Dawley rats were assigned to 3 Groups: Group A, sham operated rats as controls (n = 7); Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation (n = 7), and blood samples were taken for measurement of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) (by bioassay), and interleukin-10 (IL-10), transforming growth factor-β (TGF-β) (by ELISA). The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS: Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines (TNF-α, IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10, TGF-β) at 24 h increased significantly (P 〈 0.05) in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation (P 〈 0.05), and IL-IO, TGF-13 were inhibited at 24 h compared to Group B (P 〈 0.05). Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION: 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.展开更多
AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously i...AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice(6-12 wk old,18-22 g).When the tumors reached a size of 100 mm 3,the animals were treated as indicated,and the mice were randomly assigned to seven groups(n = 10 each).After ten days of treatment,blood samples were collected from mouse eyes,and serum was harvested by centrifugation.Mice were sacrificed,and the whole body,tumor,spleen and thymus were weighed immediately.The rate of tumor inhibition and organ indexes were calculated.The expression levels of serum cytokines,P-glycoprotein(P-GP) and multidrug resistance(MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay,Western blotting,and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction,respectively.RESULTS:The tumor inhibition rates in the treatment groups of Adriamycin(ADM) + Astragalus polysaccharides(APS)(50 mg/kg),ADM + APS(100 mg/kg),and ADM + APS(200 mg/kg) were significantly higher than in the ADM group(72.88% vs 60.36%,P = 0.013;73.40% vs 60.36%,P = 0.010;77.57% vs 60.36%,P = 0.001).The spleen indexes of the above groups were also significantly higher than in the ADM group(0.65 ± 0.22 vs 0.39 ± 0.17,P = 0.023;0.62 ± 0.34 vs 0.39 ± 0.17,P = 0.022;0.67 ± 0.20 vs 0.39 ± 0.17,P = 0.012),and the thymus indexes of the ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups were significantly higher than in the ADM group(0.20 ± 0.06 vs 0.13 ± 0.04,P = 0.029;0.47 ± 0.12 vs 0.13 ± 0.04,P = 0.000).APS was found to exert a synergistic antitumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD.The expression of interleukin-1α(IL-1α),IL-2,IL-6,and tumor necrosis factor-α(TNF-α) was significantly higher in the ADM + APS(50 mg/kg),ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups than in the ADM group;and IL-10 was significantly lower in the above groups than in the ADM group.APS could increase IL-1α,IL-2,IL-6,and TNF-α expression and decrease IL-10 levels.Compared with the ADM group,APS treatment at a dose of 50-200 mg/kg could downregulate MDR1 mRNA expression in a dose-dependent manner(0.48 ± 0.13 vs 4.26 ± 1.51,P = 0.000;0.36 ± 0.03 vs 4.26 ± 1.51,P = 0.000;0.21 ± 0.04 vs 4.26 ± 1.51,P = 0.000).The expression level of P-GP was significantly lower in the ADM + APS(200 mg/kg) group than in the ADM group(137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg,P = 0.023).CONCLUSION:APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice.This may be related to its ability to enhance the expression of IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.展开更多
Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of ...Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability 'of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.展开更多
Objective:To investigate the actions of cytokine profile in the immune cells by a seven amino acid peptide mimic from HVR1 of HCV (GQTYTSG,named 7P).Methods:The peripheral blood mononuclear cells (PBMCs) from 17 healt...Objective:To investigate the actions of cytokine profile in the immune cells by a seven amino acid peptide mimic from HVR1 of HCV (GQTYTSG,named 7P).Methods:The peripheral blood mononuclear cells (PBMCs) from 17 healthy blood donors were stimulated with 7P,and the cytokine levels in CD4+CD8-,CD4-CD8+ T cells,NK,NKT cells were analyzed by the intracellular cytokine staining.Results:The frequency of cells which secreted interferon-γ (IFN-γ) was found to be significantly increased in all cells,interleukin-10(IL-10) was significantly increased in CD4+CD8-,CD4-CD8+ T cells but decreased in NK,NKT cells,and tumor necrosis factor-α (TNF-α) was decreased in CD4+CD8-,CD4-CD8+ but increased in NK cells.Conclusion:7P could induce a cytokine profile in different immune cells in vitro and there was some difference between the CD4+CD8-,CD4-CD8+ T cells which represented the adaptive immunity cells and NK,NKT cells which represented the innate immunity cells.This kind of variation of cytokine profile might contribute to anti-virus and anti-inflammatory immune reaction.展开更多
文摘目的探讨血清中细胞因子6(IL-6)、细胞因子10(IL-10)和高敏C反应蛋白(Hs-CRP)在小儿肺炎支原体肺炎(MPP)发病中的作用及临床意义。方法采用酶联免疫吸附法(ELISA)检测MPP患儿入院时和抗炎治疗后血清中IL-6、IL-10含量。用速率散射比浊法测定Hs-CRP含量并与对照组间比较,并进行统计学分析。结果 MPP组治疗前IL-6为(19.15±1.34)pg/ml,IL-10(18.25±1.41)pg/ml,Hs-CRP(28.4±3.05)mg/L与对照组IL-6(6.32±0.57)pg/ml,IL-10(6.11±2.03)pg/ml,Hs-CRP(6.41±1.15)mg/L浓度比较差异有统计学意义(t=64.001、t=32.618、t=49.272、P<0.01);MPP组治疗第7~10 d IL-6(6.65±1.05)pg/ml,IL-10(6.89±1.66)pg/ml,Hs-CRP(6.86±1.24)mg/L浓度比对照组有所升高,但其差异无统计学意义。结论MPP患儿入院治疗前,治疗后血清IL-6、IL-10,Hs-CRP含量的变化对疾病的进展和疗效有一定指导意义,提示IL-6、IL-10和Hs-CRP在MPP发病机制中起重要作用。
文摘AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS: Male Sprague Dawley rats were assigned to 3 Groups: Group A, sham operated rats as controls (n = 7); Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation (n = 7), and blood samples were taken for measurement of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) (by bioassay), and interleukin-10 (IL-10), transforming growth factor-β (TGF-β) (by ELISA). The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS: Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines (TNF-α, IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10, TGF-β) at 24 h increased significantly (P 〈 0.05) in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation (P 〈 0.05), and IL-IO, TGF-13 were inhibited at 24 h compared to Group B (P 〈 0.05). Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION: 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.
文摘AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice(6-12 wk old,18-22 g).When the tumors reached a size of 100 mm 3,the animals were treated as indicated,and the mice were randomly assigned to seven groups(n = 10 each).After ten days of treatment,blood samples were collected from mouse eyes,and serum was harvested by centrifugation.Mice were sacrificed,and the whole body,tumor,spleen and thymus were weighed immediately.The rate of tumor inhibition and organ indexes were calculated.The expression levels of serum cytokines,P-glycoprotein(P-GP) and multidrug resistance(MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay,Western blotting,and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction,respectively.RESULTS:The tumor inhibition rates in the treatment groups of Adriamycin(ADM) + Astragalus polysaccharides(APS)(50 mg/kg),ADM + APS(100 mg/kg),and ADM + APS(200 mg/kg) were significantly higher than in the ADM group(72.88% vs 60.36%,P = 0.013;73.40% vs 60.36%,P = 0.010;77.57% vs 60.36%,P = 0.001).The spleen indexes of the above groups were also significantly higher than in the ADM group(0.65 ± 0.22 vs 0.39 ± 0.17,P = 0.023;0.62 ± 0.34 vs 0.39 ± 0.17,P = 0.022;0.67 ± 0.20 vs 0.39 ± 0.17,P = 0.012),and the thymus indexes of the ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups were significantly higher than in the ADM group(0.20 ± 0.06 vs 0.13 ± 0.04,P = 0.029;0.47 ± 0.12 vs 0.13 ± 0.04,P = 0.000).APS was found to exert a synergistic antitumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD.The expression of interleukin-1α(IL-1α),IL-2,IL-6,and tumor necrosis factor-α(TNF-α) was significantly higher in the ADM + APS(50 mg/kg),ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups than in the ADM group;and IL-10 was significantly lower in the above groups than in the ADM group.APS could increase IL-1α,IL-2,IL-6,and TNF-α expression and decrease IL-10 levels.Compared with the ADM group,APS treatment at a dose of 50-200 mg/kg could downregulate MDR1 mRNA expression in a dose-dependent manner(0.48 ± 0.13 vs 4.26 ± 1.51,P = 0.000;0.36 ± 0.03 vs 4.26 ± 1.51,P = 0.000;0.21 ± 0.04 vs 4.26 ± 1.51,P = 0.000).The expression level of P-GP was significantly lower in the ADM + APS(200 mg/kg) group than in the ADM group(137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg,P = 0.023).CONCLUSION:APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice.This may be related to its ability to enhance the expression of IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.
基金Supported by Development funds from Section of Gastroenterology/Hepatology, Internal Medicine, University of Nebraska Medical Center
文摘Alcoholic patients have a high incidence of hepatitis C virus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability 'of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.
基金Supported by the National High Technology Research and Development Program of China(863 Program,No. 2006AA022494)
文摘Objective:To investigate the actions of cytokine profile in the immune cells by a seven amino acid peptide mimic from HVR1 of HCV (GQTYTSG,named 7P).Methods:The peripheral blood mononuclear cells (PBMCs) from 17 healthy blood donors were stimulated with 7P,and the cytokine levels in CD4+CD8-,CD4-CD8+ T cells,NK,NKT cells were analyzed by the intracellular cytokine staining.Results:The frequency of cells which secreted interferon-γ (IFN-γ) was found to be significantly increased in all cells,interleukin-10(IL-10) was significantly increased in CD4+CD8-,CD4-CD8+ T cells but decreased in NK,NKT cells,and tumor necrosis factor-α (TNF-α) was decreased in CD4+CD8-,CD4-CD8+ but increased in NK cells.Conclusion:7P could induce a cytokine profile in different immune cells in vitro and there was some difference between the CD4+CD8-,CD4-CD8+ T cells which represented the adaptive immunity cells and NK,NKT cells which represented the innate immunity cells.This kind of variation of cytokine profile might contribute to anti-virus and anti-inflammatory immune reaction.