AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METH...AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.展开更多
Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglio...Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival,macrophage activation,and PI3K/Akt and JAK/STAT activation.The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups.Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2.However,protein expression was increased at 12 hours,but decreased again at 24 hours,with very low expression at 96 hours.LY294002 and AG490,which are inhibitors of the PI3K/Akt and JAK/STAT3 signal pathways,prevented upregulation of Akt and STAT3 protein expression in the retina,respectively.Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma.These results suggest that intravitreal injection of rhIL-2 could induce the PI3K/Akt and JAK/STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models.展开更多
Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genet...Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose o 8 μg/kg. However, to date, the results of the clinica trials have been disappointing. Although CD activity was reduced as measured by the CD activity index IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.展开更多
Concentration-time profiles of <sup>125</sup>I-labeled recombinant human interleukin-3 （125IrhIL-3） were de-termined by reverse phase high performance liquid chromatography （RHPLC） after intravenous an...Concentration-time profiles of <sup>125</sup>I-labeled recombinant human interleukin-3 （125IrhIL-3） were de-termined by reverse phase high performance liquid chromatography （RHPLC） after intravenous and subcutaneous ad-ministration of the drug in 16 rhesus monkeys. The initial and terminal T1/2 in plasma after intravenous of 30 μg/kg were （0. 15 ±0.13） and （2. 21 ± 0. 59） h, respectively. Terminal half-lives after 30, 90 and 180μg/kg subcutaneous （s.c.） injections were 2. 0-3.8 h. Area under concentration-time curves （AUC） following s. c. were roughly in-creased with dose, while CL5 were similar among different dosages. The absorption rates were dependent on concentra-tion at injected site. Bioavailability was about 0.7 after s.c. Rapid biodegradation was found in plasma. Distribution profiles of total radioactivity were as follows: the highest level was found in urinary system; levels in bile-enteric sys-tem, lymph nodes, bone marrow and spleen were near to that in plasma, and level in brain was the展开更多
<strong>Objective: </strong><span style="font-family:""><span style="font-family:Verdana;">To investigate the clinical effects of</span><a name="_Hlk26140...<strong>Objective: </strong><span style="font-family:""><span style="font-family:Verdana;">To investigate the clinical effects of</span><a name="_Hlk26140736"></a><span style="font-family:Verdana;"> recombinant human interleukin-2 (rhIL-2) combined with </span><a name="_Hlk26140744"></a><span style="font-family:Verdana;">Zhenqi Fuzheng and Baofukang on cervical intraepithelial neoplasia II (CINII) combined with human papilloma virus infection. </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">There were 593 patients diagnosed with CINII with HPV infection, including 296 in the control group and 297 in the experimental group. The control group was given only Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine. The experimental group was treated with rhIL-2 injection in addition to Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine which is treated for 3 months. After 3 months, Thinprep cytologic test (TCT), human papilloma virus (HPV) quantitative examination and colposcopy biopsy were reviewed. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> After 3 months of treatment, the negative conversion rate and total effective rate of HPV in the control group were 58.11% and 70.95% respectively, and the negative conversion rate and total effective rate of the experimental group were 79.46% and 90.57% respectively. There was significant difference between the two groups (p = 0.000). The curative rate of cervical lesions was significantly higher in the test group than in the control group, 89.56%, 68.91%, respectively. The statistical difference between the two groups is significant (p = 0.000). </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> It has an essential clinical value that HPV infection patients and cervical intraepithelial neoplasia II associated with </span><a name="_Hlk47768779"></a><span style="font-family:Verdana;">HPV infection patients are treated by rhIL-2 combined with Zhenqifuzheng and Baofukang, </span><a name="_Hlk47805707"></a><span style="font-family:Verdana;">which is safe, effective, non-invasive, reusable advantages. However, the long-term efficacy and side effects need to be further studied.</span></span>展开更多
[目的]探讨重组人白细胞介素-12（recombinant human interleukin-12,rhIL-12）在胰腺癌放射治疗放射防护中发挥的作用。[方法]回顾性分析52例胰腺癌患者,根据治疗方式分为单纯放疗组和rhIL-12＋放疗组。两组患者均采用射波刀治疗,放射...[目的]探讨重组人白细胞介素-12（recombinant human interleukin-12,rhIL-12）在胰腺癌放射治疗放射防护中发挥的作用。[方法]回顾性分析52例胰腺癌患者,根据治疗方式分为单纯放疗组和rhIL-12＋放疗组。两组患者均采用射波刀治疗,放射剂量30~35Gy,r IL-12＋放疗组放疗后予以150ng/kg rhIL-12干预治疗。两组分别于0h、12h、3d、7d、14d、21d、28d采用流式细胞术检测两组患者细胞免疫功能相关指标CD4/CD8比值、CD45、CD56数值变化;ELISA法检测血清细胞因子IFN-γ表达水平;分析评价两组患者外周血细胞计数变化、近期治疗疗效和胃肠道相关不良反应。[结果]rhIL-12＋放疗组患者免疫相关分子CD4/CD8比值、CD45和CD56表达12h内均存在一过性降低现象,随治疗时间的推移逐渐回升,于治疗第14d达到峰值且恢复,改善趋势明显优于单纯放疗组（P〈0.05）;细胞因子IFN-γ表达随时间变化逐渐递增,于14d达峰值,较单纯放疗组具有显著性差异（P〈0.05）。血液标本检测显示两组患者治疗前红细胞（RBC）、白细胞（WBC）、血小板（PLT）、中性粒细胞（NEUT）计数以及血红蛋白（Hb）含量均无显著性差异（P〉0.05）;在治疗14d时rhIL-12＋放疗组患者WBC、PLT和NEUT计数较单纯放疗组均具显著性差异（P〈0.05）,而RBC计数和Hb含量则差异无统计学意义（P〉0.05）;rhIL-12＋放疗组患者近期治疗疗效显著（P=0.046）;两组患者胃肠道不良反应主要表现为恶心呕吐和腹泻,rhIL-12＋放疗组发生率均低于单纯放疗组（P=0.001;P=0.012）。[结论]rhIL-12可有效地促进胰腺癌放射治疗患者造血功能和免疫机能的恢复和重建,并能降低放射治疗不良反应的发生率,提高治疗疗效。展开更多
文摘AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.
基金the New Century Excellent Talents Project Grant by the Ministry of Education of China,No.NCET-06-0677the Natural Science Foundation of Hu-nan Province,No.05JJ30051
文摘Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival,macrophage activation,and PI3K/Akt and JAK/STAT activation.The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups.Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2.However,protein expression was increased at 12 hours,but decreased again at 24 hours,with very low expression at 96 hours.LY294002 and AG490,which are inhibitors of the PI3K/Akt and JAK/STAT3 signal pathways,prevented upregulation of Akt and STAT3 protein expression in the retina,respectively.Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma.These results suggest that intravitreal injection of rhIL-2 could induce the PI3K/Akt and JAK/STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models.
基金Supported by The Ministry of Business,Innovation and EmploymentDutch Digestive Foundation
文摘Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose o 8 μg/kg. However, to date, the results of the clinica trials have been disappointing. Although CD activity was reduced as measured by the CD activity index IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.
文摘Concentration-time profiles of <sup>125</sup>I-labeled recombinant human interleukin-3 （125IrhIL-3） were de-termined by reverse phase high performance liquid chromatography （RHPLC） after intravenous and subcutaneous ad-ministration of the drug in 16 rhesus monkeys. The initial and terminal T1/2 in plasma after intravenous of 30 μg/kg were （0. 15 ±0.13） and （2. 21 ± 0. 59） h, respectively. Terminal half-lives after 30, 90 and 180μg/kg subcutaneous （s.c.） injections were 2. 0-3.8 h. Area under concentration-time curves （AUC） following s. c. were roughly in-creased with dose, while CL5 were similar among different dosages. The absorption rates were dependent on concentra-tion at injected site. Bioavailability was about 0.7 after s.c. Rapid biodegradation was found in plasma. Distribution profiles of total radioactivity were as follows: the highest level was found in urinary system; levels in bile-enteric sys-tem, lymph nodes, bone marrow and spleen were near to that in plasma, and level in brain was the
文摘<strong>Objective: </strong><span style="font-family:""><span style="font-family:Verdana;">To investigate the clinical effects of</span><a name="_Hlk26140736"></a><span style="font-family:Verdana;"> recombinant human interleukin-2 (rhIL-2) combined with </span><a name="_Hlk26140744"></a><span style="font-family:Verdana;">Zhenqi Fuzheng and Baofukang on cervical intraepithelial neoplasia II (CINII) combined with human papilloma virus infection. </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">There were 593 patients diagnosed with CINII with HPV infection, including 296 in the control group and 297 in the experimental group. The control group was given only Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine. The experimental group was treated with rhIL-2 injection in addition to Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine which is treated for 3 months. After 3 months, Thinprep cytologic test (TCT), human papilloma virus (HPV) quantitative examination and colposcopy biopsy were reviewed. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> After 3 months of treatment, the negative conversion rate and total effective rate of HPV in the control group were 58.11% and 70.95% respectively, and the negative conversion rate and total effective rate of the experimental group were 79.46% and 90.57% respectively. There was significant difference between the two groups (p = 0.000). The curative rate of cervical lesions was significantly higher in the test group than in the control group, 89.56%, 68.91%, respectively. The statistical difference between the two groups is significant (p = 0.000). </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> It has an essential clinical value that HPV infection patients and cervical intraepithelial neoplasia II associated with </span><a name="_Hlk47768779"></a><span style="font-family:Verdana;">HPV infection patients are treated by rhIL-2 combined with Zhenqifuzheng and Baofukang, </span><a name="_Hlk47805707"></a><span style="font-family:Verdana;">which is safe, effective, non-invasive, reusable advantages. However, the long-term efficacy and side effects need to be further studied.</span></span>
文摘[目的]探讨重组人白细胞介素-12（recombinant human interleukin-12,rhIL-12）在胰腺癌放射治疗放射防护中发挥的作用。[方法]回顾性分析52例胰腺癌患者,根据治疗方式分为单纯放疗组和rhIL-12＋放疗组。两组患者均采用射波刀治疗,放射剂量30~35Gy,r IL-12＋放疗组放疗后予以150ng/kg rhIL-12干预治疗。两组分别于0h、12h、3d、7d、14d、21d、28d采用流式细胞术检测两组患者细胞免疫功能相关指标CD4/CD8比值、CD45、CD56数值变化;ELISA法检测血清细胞因子IFN-γ表达水平;分析评价两组患者外周血细胞计数变化、近期治疗疗效和胃肠道相关不良反应。[结果]rhIL-12＋放疗组患者免疫相关分子CD4/CD8比值、CD45和CD56表达12h内均存在一过性降低现象,随治疗时间的推移逐渐回升,于治疗第14d达到峰值且恢复,改善趋势明显优于单纯放疗组（P〈0.05）;细胞因子IFN-γ表达随时间变化逐渐递增,于14d达峰值,较单纯放疗组具有显著性差异（P〈0.05）。血液标本检测显示两组患者治疗前红细胞（RBC）、白细胞（WBC）、血小板（PLT）、中性粒细胞（NEUT）计数以及血红蛋白（Hb）含量均无显著性差异（P〉0.05）;在治疗14d时rhIL-12＋放疗组患者WBC、PLT和NEUT计数较单纯放疗组均具显著性差异（P〈0.05）,而RBC计数和Hb含量则差异无统计学意义（P〉0.05）;rhIL-12＋放疗组患者近期治疗疗效显著（P=0.046）;两组患者胃肠道不良反应主要表现为恶心呕吐和腹泻,rhIL-12＋放疗组发生率均低于单纯放疗组（P=0.001;P=0.012）。[结论]rhIL-12可有效地促进胰腺癌放射治疗患者造血功能和免疫机能的恢复和重建,并能降低放射治疗不良反应的发生率,提高治疗疗效。
