Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients

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.

Recombinant human interleukin-11 for treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer

Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and non-randomized controlled clinical study. When the platelet counts was under 75 × 10^9/L after chemotherapy, rhlL-11 was administered 25 μg/（kg·d） as a daily SC injection last for 7-14 days, or discontinued when platelet counts 〉 100 × 10^9/L. Results： Seventysix patients were enrolled into this study. The treatment group and the control group had thirty-eight cases, respectively. The mean recovery time to PLT ≥ 100 × 10^9/L was 8.1 days in treatment group, while in control group was 12.2 days （P 〈 0.01）. Moreover, the mean recovery time from PLT 〈_ 50 × 10^9/L to 〉 100 × 10^9/L was 8.9 days in treatment group, while in control group was 12.9 days （P 〈 0.05）. There was a statistical difference between the two groups. Major side effects included edema, fever, articular muscle soreness, but they were all mild and well tolerable. Conclusion： rhIL-11 can be safely and effectively used for the treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer.

Neuronal changes in the retinal ganglion cell layer following recombinant human interleukin-2 intravitreal injection in a rat model of chronically elevated intraocular pressure

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.

Up-regulation interleukin-6 and interleukin-8 by activated protein C in lipopolysaccharide-treated human umbilical vein endothelial cells

Objective: To investigate the effect of activated protein C (APC) on inflammatory responses in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). Methods: The second passage of collagenase digested HUVEC was divided into the following groups: serum free medium control group (SFM control), phosphate buffer solution control group (PBS control), LPS group with final concentration of 1 μg/ml (LPS group), APC group with final concentration of 7 μg/ml, Pre-APC group (APC pretreatment for 30 min prior to LPS challenge), and Post-APC group (APC administration 30 min after LPS challenge). Supernatant was harvested at 0, 4, 8, 12 and 24 h after LPS challenge. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) levels were analyzed with ELISA. Cells were harvested at 24 h after LPS challenge, and total RNA was extracted. Mes-senger RNA levels for IL-6 and IL-8 were semi-quantitatively determined by RT-PCR. Results: Compared with control group, IL-6 and IL-8 levels steadily increased 4 to 24 h after LPS stimulation. APC treatment could increase LPS-induced IL-6 and IL-8 production. The mRNA levels of IL-6 and IL-8 exhibited a similar change. Conclusion: APC can further increase the level of IL-6 and IL-8 induced by LPS. The effect of these elevated cytokines is still under investigation.

Upregulation of stromal cell-derived factor-1 alpha/CXCR4 axis-induced migration of human neural progenitors by tumor necrosis factor-alpha and interleukin-8

BACKGROUND： Studies of several animal models of central nervous system diseases have shown that neural progenitor cells （NPCs） can migrate to injured tissues. Stromal cell-derived factor 1 alpha （SDF-la）, and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE： To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in SDF-1α/CXCR4 axis-induced migration of NPCs. DESIGN, TIME AND SETTING： An in vitro, randomized, controlled, cellular and molecular biology study was performed at the Laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007. MATERIALS： SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R＆D Systems, USA. TNF-αwas purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research Institute of Soochow University. METHODS： NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES： The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry. RESULTS： Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs （P 〈 0.01）, and 20 ng/mL produced the highest levels of migration. Anti-human CXCR4 fusion antibody significantly blocked the chemotactic effect （P 〈 0.05）. Flow cytometry results showed that treatment with TNF-α and IL-8 resulted in increased CXCR4 expression and greater chemotaxis efficiency of NPCs towards SDF-1α（P 〈 0.01）. CONCLUSION： These results demonstrated that SDF-la significantly attracted NPCs in vitro, and neutralizing anti-CXCR4 antibody could block part of this chemotactic function. TNF-α and IL-8 increased chemotaxis efficiency of NPCs towards the SDF-1αgradient by upregulating CXCR4 expression in NPCs.

Expression levels of pro-inflammatory interleukin-8 and certain antimicrobial peptides in concurrent with bacterial conjunctivitis

AIM:To detect the quantitative expression levels of the pro-inflammatory interleukin-8(IL8),antimicrobial peptides human beta defense-2(HBD2),and human beta defense-3(HBD3)genes in bacterial conjunctivitis.METHODS:The human conjunctival epithelial cells were obtained using the impression cytology technique from healthy controls and patients.The genes expression levels were determined utilizing a reverse transcription quantitative polymerase chain reaction(RT-q PCR).The contribution of causative agent type,the number of isolates and severity of clinical features,in the increase of genes expression was also determined.RESULTS:The RT-q PCR showed that IL8,HBD2,and HBD3 expression increased in bacterial conjunctivitis as compared to healthy control(P<0.001).In gram-negative bacterial conjunctivitis,HBD2 was highly up-regulated(P<0.001)compared to other types of bacterial conjunctivitis.In mixed bacterial conjunctivitis,a direct correlation between HBD2 up-regulation and HBD3 up-regulation was observed(P<0.05).The severity of clinical features was related to the up-regulation of IL8 and HBD2(P<0.05).CONCLUSION:IL8,HBD2,and HBD3 are immuneeffectors in infectious conjunctivitis.HBD2 is active during different bacterial conjunctivitis but is more released with gram-negative bacteria compared to gram-positive bacteria.HBD3 is an obvious defender in different bacterial conjunctivitis.

重构型人caspase-8基因的表达及其对HeLa细胞生长的影响

目的 克隆人ｃａｓｐａｓｅ－８催化结构域基因片段，并将其改建成２种大、小亚基基因次序颠倒的重构型人ｃａｓｐａｓｅ－８基因，转染ＨｅＬａ细胞，观察重构型人ｃａｓｐａｓｅ－８基因的表达及其对ＨｅＬａ细胞生长的影响。 方法 用ＲＴ－ＰＣＲ法，克隆人ｃａｓｐａｓｅ－８催化结构域基因片段，经重组ＰＣＲ改造，构建大、小亚基基因次序颠倒的重构型人ｃａｓｐａｓｅ－８基因。将其克隆入绿色荧光蛋白（ＧＦＰ）真核表达载体ｐＩＲＥＳ２－ＥＧＦＰ，转染ＨｅＬａ细胞，用荧光显微镜和倒置显微镜镜观察细胞的形态和结构。 结果用ＲＴ－ＰＣＲ法，成功地克隆了人ｃａｓｐａｓｅ－８催化结构域基因片段，构建了３种重构型人 ｃａｓｐａｓｅ－８基因及其真核表达载体。转染ＨｅＬａ细胞后，重构型人ｃａｓｐａｓｅ－８基因的表达可导致ＨｅＬａ细胞死亡。 结论重构型人ｃａｓｐａｓｅ－８基因在ＨｅＬａ细胞中的表达可以有效地引起ＨｅＬａ细胞死亡。

人重组IL-8在大肠杆菌中表达及其活性检测

本文报道了利用基因工程技术在大肠杆菌中表达人重组白细胞介素8(rh(?)。将质粒pGEM-hIL-8中的IL-8cDNA片段亚克隆到表达载体pMS31b中,在大肠杆菌中成功地高效表达出人IL-8融合蛋白,表达产物具有体内、体外对小鼠中性粒细胞的趋化活性。表明N端连入一段细菌蛋白并不影响IL-8的趋化活性。

含绿色荧光蛋白基因与人疱疹病毒8型K12基因重组真核表达载体的构建

目的:构建含绿色荧光蛋白(GFP)基因与人疱疹病毒8型K12基因的重组真核表达载体。方法:将人疱疹病毒8型(HHV-8)K12基因插入到真核表达质粒pCR3.1的EcoRI和XhoI位点,构建重组质粒pCR-K12;PCR扩增GFP基因,将GFP基因插入到重组质粒pCR-K12中K12上游的KpnI和EcoRI位点中,获得重组表达质粒pCR-GFP-K12。结果:重组表达质粒pCR-GFP-K12的酶切鉴定符合预期结果,此重组质粒中的K12与GFP融合表达并受上游启动子pCMV控制。结论:重组表达质粒pCR-GFP-K12已构建成功,为研究K12的生物学活性及其作用机制打下基础。

重组人乳铁蛋白对Tca8113细胞中促炎性反应细胞因子IL-6和IL-8蛋白表达的影响

目的:研究重组人乳铁蛋白(rhLF)对口腔鳞癌Tca8113细胞中促炎症反应细胞因子IL-6和IL-8表达的影响,探讨其抑制肿瘤细胞生长的可能机制。方法:体外培养口腔鳞癌Tca8113细胞,用rhLF处理体外培养的Tca8113细胞,应用酶联免疫吸附试验、免疫组织化学方法检测50 mg·L-1rhLF和100 mg·L-1rhLF对Tca8113细胞分泌的IL-6和IL-8蛋白表达的影响。结果:随着rhLF浓度的增加,培养上清中的IL-6和IL-8含量逐渐下降;100 mg·L-1rhLF组培养上清中IL-6和IL-8水平明显下降,与正常对照组比较差异有统计学意义(P<0.05)。免疫组化染色,IL-6、IL-8在Tca8113细胞有表达,与对照组比较,50 mg.L-1rhLF组IL-6、IL-8在Tca8113细胞的表达明显下降,表现为弱表达或不表达。结论:rhLF在体外可以特异性地抑制口腔鳞癌Tca8113细胞中IL-6和IL-8的生成,诱导肿瘤细胞炎症性环境的改变,达到抑制肿瘤生长的目的。

人重组白细胞介素-8的快速纯化

报道一种快速人重组IL-8纯化方法，大肠杆菌表达的IL-8包涵体经尿素变性后，直接用DEAE柱和SephadexG50柱纯化。纯化的hIL-8经FPLC鉴定，纯度达90%以上。该法为实验室快速、简便纯hIL-8提供了新的技术路线。

重构型人caspase-8基因原核表达载体的构建及其表达

目的 :构建三种重构型人caspase - 8基因的原核表达载体 ,转染大肠杆菌并诱导其表达。方法 :将人caspase- 8催化结构域基因及两种大、小亚基基因次序颠倒的重构型人caspase - 8基因克隆入原核表达载体pBV2 2 0 ,转染大肠杆菌并诱导表达。结果 :成功构建了三种重构型人caspase- 8基因的原核表达载体。转染大肠杆菌后 ,经温度诱导 ,重构型人caspase - 8基因获得了高效的表达。结论 :在大肠杆菌中成功表达了三种重构型人caspase - 8基因。

重组人促红细胞生成素对兔脊髓缺血/再灌注损伤后白细胞介素8表达的影响

目的探讨重组人促红细胞生成素(rHuEPO)对兔脊髓神经细胞缺血/再灌注损伤后白细胞介素8(IL-8)表达的影响。方法 44只健康成年新西兰大白兔随机分为3组:假手术组(4只),对照组(20只),rHuEPO处理组(20只),对照组与rHuEPO处理组分别于再灌注6 h,12 h,24 h、48 h、7 d后时间点随机处死4只动物,取L3～L5节段脊髓组织用霉菌抗生物素蛋白-过氧化酶免疫组化染色法(S-P法)及兔抗人IL-8 ELISA试剂盒检测脊髓组织内IL-8的表达。结果 IL-8在无损伤脊髓中即见有表达。随着缺血及再灌注进程的加重,组织中IL-8阳性表达强度逐渐增加。脊髓损伤后24 h表达明显上调并达高峰;高表达持续至损伤后7 d;两组间IL-8水平的变化趋势相同,但在各时间点rHuEPO处理组兔脊髓组织IL-8的含量均低于对照组(P<0.05)。结论 rHuEPO具有抑制脊髓组织炎症反应的作用,能明显抑制兔脊髓缺血/再灌注损伤后的IL-8表达。

重组人粒细胞集落刺激因子调节IL-27和IRF8表达诱导供受者免疫耐受机制的初步研究

目的 rhG-CSF既是造血干细胞动员剂,也是免疫耐受诱导剂,可减轻移植物抗宿主病(GVHD);干扰素调节因子8(IRF8)拮抗小鼠RORγt的作用,可以抑制小鼠初始T细胞向Th17细胞分化;本文旨在研究rhG-CSF动员对IRF8基因表达及蛋白水平、外周血Th17和Treg细胞的比例和Th17分化的负性调控因子IL-27的调节作用。方法 采集10名造血干细胞移植供者rhG-CSF动员前后(第5天)外周血,通过免疫磁珠法分离CD4+T细胞,qRT-PCR及Western blotting检测CD4+T细胞IRF8基因及蛋白水平,流式细胞术检测Th17(CD3+CD8-IL-17+)和Treg细胞(CD4+CD25+Foxp3+)比例,ELISA法检测血清中IL-17及IL-27的浓度。结果 动员前、后外周血外周血单个核中细胞的比例(%):Th17细胞(2.597±1.993)%比(0.355±0.129)%(P<0.01)),Treg细胞(0.468±0.522)%比(1.491±1.216)%(P<0.01);动员前、后IL-17A(pg/ml):(21.75±18.77)pg/ml比(15.53±10.89)pg/ml(P<0.01);动员前、后IL-27(pg/ml):(5 180.06±1 860.75)pg/ml比(3 806.56±1 658.89)pg/ml(P<0.01)。IRF8基因表达在动员后基因表达相对增加1.69倍,IRF8蛋白在动员后比动员前表达显著增加。结论 rhG-CSF抑制供者外周血Th17细胞、促进Treg细胞群分化,诱导免疫耐受,可能与rhG-CSF促进CD4+T细胞中IRF8、IL-27和IRF8负性调控Th17细胞分化有关。

Why interleukin-10 supplementation does not work in Crohn's disease patients

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.

重组人α8型干扰素的纯化与鉴定

采用酵母表达载体进行重组人α８型干扰素（ＨｕＩＦＮα８）的表达，该表达菌株可将重组α８型干扰素分泌进入培养基中，回收培养基进行纯化，然后利用超滤浓缩，先过Ｓ．ＳｅｐｈａｒｏｓｅＦＦ柱，再进行ＤＥＡＥＳｅｐｈａｒｏｓｅＦＦ层析和Ｇ２５脱盐，最后用高效液相ＨＰＬＣ，ＳＤＳＰＡＧＥ丙烯酰胺凝胶电泳及肽图等方法对纯化产品进行鉴定。采用以上两步纯化方法纯化酵母分泌表达的重组人α８型干扰素纯度可达９５％以上，其比活性为３０×１０８ｕ／ｍｇ。

Functional recovery and microenvironmental alterations in a rat model of spinal cord injury following human umbilical cord blood-derived mesenchymal stem cells transplantation

BACKGROUND： Transplantation of human umbilical cord blood-derived mesenchymal stem cells （MSCs） has been shown to benefit spinal cord injury （SCI） repair. However, mechanisms of microenvironmental regulation during differentiation of transplanted MSCs remain poorly understood. OBJECTIVE： To observe changes in nerve growth factor （NGF）, brain-derived neurotrophic factor （BDNF）, and interleukin-8 （IL-8） expression following transplantation of human umbilical cord-derived MSCs, and to explore the association between microenvironment and neural functional recovery following MSCs transplantation. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Soochow University from April 2005 to March 2007. MATERIALS： Human cord blood samples were provided by the Department of Gynecology and Obstetrics, First Affiliated Hospital of Soochow University. Written informed consent was obtained. METHODS： A total of 62 Wister rats were randomly assigned to control （n = 18）, model （n = 22, SCI ＋ PBS）, and transplantation （n = 22, SCI ＋ MSCs） groups. The rat SCI model was established using the weight compression method. MSCs were isolated from human umbilical cord blood and cultured in vitro for several passages. 5-bromodeoxyuridine （BrdU）-Iabeled MSCs （24 hours before injection） were intravascularly transplanted. MAIN OUTCOME MEASURES： The rats were evaluated using the Basso, Beattie and Bresnahan （BBB） locomotor score and inclined plane tests. Transplanted cells were analyzed following immunohistochemistry. Enzyme-linked immunosorbant assay was performed to determine NGF, BDNF, and IL-8 levels prior to and after cell transplantation. RESULTS： A large number of BrdU-positive MSCs were observed in the SCI region of the transplantation group, and MSCs were evenly distributed in injured spinal cord tissue 1 week after transplantation. BBB score and inclined plane test results revealed significant functional improvement in the transplantation group compared to the model group （P 〈 0.05）, which was maintained for 2-3 weeks. Compared to the model group, NGF and BDNF levels were significantly increased in the injured region following MSCs transplantation at 3 weeks （P 〈 0.05）, but IL-8 levels remained unchanged （P 〉 0.05）. CONCLUSION： MSCs transplantation increased NGF and BDNF expression in injured spinal cord tissue. MSCs could promote neurological function recovery in SCI rats by upregulating NGF expression and improving regional microenvironments.

Impact of endoscopically minimal involvement on IL-8 mRNA expression in esophageal mucosa of patients with non-erosive reflux disease

AIM:Little has been known about the pathogenesis of non- erosive reflux disease(NERD).Recent studies have implicated interleukin 8(IL-8)in the development and progression of gastroesophgeal reflux disease(GERD).The purpose of this study was to determine IL-8 RNA expression levels in NERD patients with or without subtle mucosal changes. METHODS:We studied 26 patients with NERD and 13 asymptomatic controls.Biopsy sample was taken from the esophagus 3 cm above the gastroesophageal junction and snap frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction(PCR).We also examined mRNA expression of IL-8 receptors,CXCR-1 and -2 by reverse transcriptase PCR.The patients were endoscopically classified into grade M(mucosal color changes without visible mucosal break)and N(neither minimal involvement nor mucosal break)of the modified Los Angeles classification. RESULTS:The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of NERD patients than those in esophageal mucosa of the controls.There was a significant difference in IL-8 mRNA levels between grades M and N.The CXCR-1 and -2 mRNAs were constitutively expressed in esophageal mucosa.CONCLUSION: Our results suggest that high IL-8 levels in esophageal mucosa may be involved in the pathogenesis of NERD through interaction with its receptors. NERD seems to be composed of a heterogeneous population in terms of not only endoscopically minimal involvement but also immune and inflammatory processes.

rhC5a诱导PBMC产生IL-8与PKC的关系

目的:研究PKC在rhC5a诱导外周血单个核细胞(PBMC)产生IL-8中的作用。方法:将PBMC分别与rhC5a、PMA、Cheleythrine、 Calphostin C、Dequalinium孵育24 h,取上清用法测定IL-8。将PBMC分别与rhC5a、PMA孵育,按一定时间间隔收集细胞测定 PKC活性。用 Cheleythrine、Calphostin C、Dequalinium预处理 PBMC,然后再以rhC5a诱导测定其 PKC活性。结果:PBMC经rhC5a诱导后IL-8产生水平增加,同时PKC活性呈双峰型增高;PBMC经PMA诱导后不仅PKC活性增高,而且IL-8产生水平也增加;Cheleythrine、Calphostin C、Dequalinium能抑制rhC5a介导的PBMC PKC活性和IL-8产生水平增高。结论:PKC参与rhC5a诱导PBMC产生IL-8细胞内信号转导过程。

A multiple-dose pharmacokinetics of polyethylene glycol recombinant human interleukin-6 (PEG-rhIL-6) in rats

Radiation therapy has been widely applied in cancer treatment.However,it often causes thrombocytopenia (deficiency of white blood cells) as an adverse effect.Recombinant human interleukin-6 (rhIL-6) has been found to be a very effective way against this thrombocytopenia,but IL-6 has low stability in blood,which reduces its efficacy.To increases the stability and half-life of rhIL-6,it was modified by polyethylene glycol (PEG).The pharmacokinetics and the tissue distribution of PEG-rhIL-6 labeled with 125I were examined after subcutaneous injection in rats.The pharmacokinetic pattern of PEG-rhIL-6 was defined with linear-kinetics,and we fitted a one-compartment model with half-lives of 10.44–11.37 h (absorption,t1/2Ka) and 19.77–21.53 h (elimination,t1/2Ke),and peak concentrations at 20.51–21.96 h (tpeak) in rats.Half-lives and tpeak of PEG-rhIL-6 were longer than those of rhIL-6 previously reported.In the present study,for deposition of PEG-rhIL-6 in rats,the tissue distribution examination showed that blood was the major organ involved,rather than liver.However,as to the elimination of PEG-rhIL-6,the major organ was the kidney.The excretion fraction of the injection dose recovered from urine was 23.32% at 192 h after subcutaneous administration.Less than 6% of PEG-rhIL-6 was eliminated via the feces at 192 h.These results indicate that PEG-rhIL-6 is a good candidate drug formulation for patients with cancer.