重组人白细胞介素-11不良反应的临床研究

目的:观察重组人白细胞介素-11(rhIL-11)在临床应用中的不良反应.方法:选择经病理学确诊的住院恶性实体瘤46例,随机分为观察组22例及对照组24例;观察组化疗后24 h开始应用rhIL-11,对照组应用安慰药.结果:rhIL-11相关不良反应有注射部位反应、结膜充血、头晕、乏力,以及肌肉和(或)骨痛等,程度Ⅰ～Ⅲ度;发生rhlL-11相关毛细血管渗漏综合征死亡1例.结论:rhIL-11临床使用安全,但个别病例可发生严重不良反应.     

rhIL-11对正常IEC-6细胞的增殖及细胞周期的影响

目的通过研究重组人白介素11(rhIL-11)对正常IEC-6细胞增殖、细胞周期及其IL-11受体表达的影响,探讨IL-11对小肠上皮细胞的调控作用以及相关机制。方法利用MTT法检测rhIL-11对正常IEC-6细胞增殖的影响,通过流式细胞仪检测细胞周期的变化,并采用Westem blot方法检测IEG-6细胞表面IL-11受体α链的表达情况。结果rhIL-11可引起正常IEC-6细胞发生增殖抑制和明显的G／G1期阻滞,并诱导细胞表面IL-11受体α链表达增加。结论rhIL-11可能通过与IEG-6细胞表面特异性受体结合,从而启动胞浆内信号转导通路,引起细胞效应。     

IL-11对造血的刺激作用及其在辐射损伤治疗中的应用

体内外实验结果表明,IL-11(白细胞介素-11)可刺激骨髓巨核系、粒系和红系造血祖细胞的增殖,升高外周血小板、白细胞和红细胞数。因此,IL-11作为一种新的刺激骨髓造血细胞增殖的细胞因子具有它的特殊价值,可用于平时辐射事故病人和核战时伤员的救治,也可用于癌症患者放、化疗后造血功能低下的治疗,具有广阔的临床应用前景。     

细胞因子联合对4.5Gyγ射线照射比格犬造血损伤的治疗作用

目的 观察细胞因子组合对4.5 Gy γ射线照射比格犬造血系统损伤的治疗效果,为极重度骨髓型急性放射病的临床救治提供实验依据。方法 16只比格犬均给予4.5 Gy ⁶⁰Co γ射线全身照射,随机分为照射对照、综合对症和细胞因子3组。细胞因子组动物在综合对症支持治疗的基础上应用rhG-CSF、rhIL-11和rhIL-2联合治疗。2 d检测1次外周血象,分别于照射前4 d,照射后1和45 d收集骨髓和外周血进行造血细胞集落培养,制备胸骨病理切片观察组织形态学改变。结果 照射后各组动物外周血各类细胞数急剧下降,细胞因子联合治疗可提高白细胞最低值(1.04×10⁹/L,而照射对照组和综合对症组分别为0.28×10⁹/L和0.68×10⁹/L),缩短血小板减少持续时间(细胞因子组24 d,综合对症组33 d),使红细胞维持在正常值范围;照射后1 d骨髓及外周血中造血干细胞集落形成率明显下降,照射后45 d 2个治疗组造血干细胞集落数均恢复为照射前水平;照射对照组动物骨髓造血细胞完全消失,细胞因子治疗使得骨髓造血功能完全恢复,与照射前水平比较差异无统计学意义。结论 rhG-CSF、rhIL-11和rhIL-2联合应用可提高极期时外周血白细胞最低值,加速白细胞、血小板和红细胞恢复,促进4.5 Gy γ射线照射犬体内残留造血干/祖细胞的增殖、分化和成熟,从而加速造血功能的重建。rhG-CSF、 rhIL-11和rhIL-2不失为治疗极重度骨髓型急性放射病的有效措施。     

鼻咽癌中白细胞介素-10、白细胞介素-12检测及其意义

目的检测鼻咽癌患者白细胞介素-10（interleukin-10,IL-10）及白细胞介素-12（interleukin-12,IL-12）浓度。方法用酶联免疫法（Enzyme Linked Immunosorbent Assay,ELISA）检测43例鼻咽癌患者血清IL-10及IL—12浓度,并用22例健康成年人血清作为对照。结果鼻咽癌组IL—10浓度明显高于对照组,鼻咽癌组IL—12浓度明显低于对照组,IL-10浓度在晚期T分期组（T3／T4）明显高于早期T分期组（Ⅰ／Ⅱ）W〈0．01）、晚期临床分期组（Ⅲ/Ⅳ）明显高于早期临床分期组（Ⅰ／Ⅱ）,但在不同性别、年龄组及有无淋巴结转移组浓度差异无统计学意义（P〉0．05）。而IL-12在晚期T分期组（T3／T4）N显低于早期T分期组（Ⅰ／Ⅱ）（P〈0．01）、晚期临床分期组（Ⅲ/Ⅳ）明显低于早期临床分期组（Ⅰ/Ⅱ）,但在不同性别、年龄组及有无淋巴结转移组浓度差异无统计学意义（P〉0．05）。且IL-10及IL-12浓度呈负相关关系。结论鼻咽癌中高浓度的IL-10可能抑制IL-12的产生,帮助肿瘤细胞免疫逃避,损害机体肿瘤免疫,从而促进肿瘤发展。     

不同牙周健康状况血清IL-21和IL-6检测的临床意义

目的探讨不同牙周健康状况者血清白细胞介素21(IL-21)、白细胞介素6(IL-6)水平的变化及其意义。方法选择符合标准的受试者70例,其中正常组,轻度、中度及重度牙周炎组分别为10例,20例,20例,20例;采用双抗体夹心酶联免疫吸附试验(ELISA)、放射免疫法检测受试者血清IL-21与IL-6水平。结果牙周炎组患者血清IL-21和IL-6的表达高于正常组(P<0.05);重度牙周炎组患者血清IL-21和IL-6表达分别高于轻度、中度牙周炎组(P<0.05);血清IL-21、IL-6表达强度与牙周病严重程度的变化呈正相关(r=0.653,P<0.05)。结论检测牙周病患者血清IL-21和IL-6水平的变化对探讨其发病机制、预防和指导用药具有重要的临床价值。     

Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles

Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.     

Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles

Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.     

重组人白细胞介素-11和姜黄素对中子照射致小鼠肠道损伤的治疗作用

目的 探讨重组人白细胞介素-11(rhIL-11)和姜黄素对中子照射致小鼠肠道损伤的治疗作用。方法 选取二级雄性BALB/c小鼠140只,随机分为健康对照组(20只)、单纯照射组(60只)、IL-11治疗组(30只)和姜黄素治疗组(30只)。单纯照射组小鼠采用3 Gy中子全身均匀照射,两个治疗组于照射后即日分别腹腔注射500μg·kg^-1·d^-1的rhIL-11或200 mg·kg^-1·d^-1的姜黄素,每天1次,连续给药5d。观察各组动物的死亡率。照射后6 h、1、3和5 d分别处死健康对照组和单纯照射组动物,3和5 d分别处死两个治疗组动物。取空肠标本,用HE深色、核仁组成区嗜银蛋白染色、Feulgen氏染色和图像死亡分析等,检测空肠病理形态变化、空肠上皮细胞核内嗜银蛋白含量和DNA含量变化。结果 照后5d,单纯照射组小鼠全部死亡,rhIL-11治疗组存活剩余2只,姜黄素治疗组存活剩余3只。3Gy中子照射后6 h～3 d内,空肠黏膜大面积坏死脱落,3d偶见隐窝细胞再生,5d见较多新生隐窝;IL-11治疗组在照后3d隐窝再生较明显,5d见大量新生绒毛;姜黄素治疗组在照后3d隐窝有部分再生,5d可见新生绒毛,排列结构较IL-11治疗组紊乱,绒毛高度较IL-11治疗组略低。照后5d,两个治疗组小鼠空肠上皮细胞AgNOR含量和DNA含量均高于单纯照射组(F＝0.015～0.035,P<0.05)。结论 3 Gy中子照射引起小鼠空肠明显损伤,rhIL-11和姜黄素治疗可减轻损伤并促进肠道上皮再生修复,对中子辐射肠上皮损伤具有保护作用。     

rhIL-11对外周血小板数及造血祖细胞增殖的影响

观察rhIL-11在体外对人骨髓造血祖细胞集落形成和对3.0Gy照射猕猴的外周血小板数及骨髓造血祖细胞恢复的影响。结果显示，rhIL-11可明显提高照射猴外周血小板数的最低值，缩短血小板最低值的持续时间，加速血小板数的恢复，但未见到血小板数与rhIL-11剂量间的明显关系。rhIL-11不仅直接刺激CFU－MK增殖和分化，而且还可促进CFU－GM、CFU－e、BFU－e及早期的CFU－Mix的增殖。提示rhIL-11可能是治疗血小板减少和骨髓再生不良的一个有效药物。     

白细胞介素－11基因治疗促进放射损伤小鼠造血恢复的实验研究

白细胞介素－１１（Ｉｎｔｅｒｌｅｕｋｉｎ－１１，ＩＬ－１１）是一种新的造血生长因子，体内、外实验结果显示ＩＬ－１１具有显著的造血促进作用，它能作用于早期的造血干细胞及祖细胞，促进其增殖和分化。为了探讨ＩＬ－１１基因治疗放射损伤后造血恢复的促进作用，我们构建了含人ＩＬ－１１ｃＤＮＡ的逆转录病毒载体，并转染小鼠成纤维细胞系ＮＩＨ－３Ｔ３，经筛选获得３株高表达ＩＬ－１１的转染细胞亚克隆，用高表达ＩＬ－１１的转染细胞作为载体细胞，进行了ＩＬ－１１基因治疗对放射损伤小鼠造血系统影响的实验研究。结果表明ＩＬ－１１基因治疗能明显缩短亚致死量放射损伤小鼠白细胞降低的时间，促进外周血白细胞、血小板和红细胞压积的恢复。提示ＩＬ－１１基因治疗对放射损伤造成的造血功能低下具有潜在的应用价值。     

rhIL-11对中子照射小鼠肠损伤的治疗作用

目的研究重组人白介素11(rhIL-11)对中子照射小鼠小肠上皮损伤及细胞周期的影响。方法采用裂变中子照射小鼠模型，观察rhIL-11对照射后小鼠小肠上皮形态、隐窝细胞坏死和细胞增生的影响，用流式细胞仪检测小鼠小肠上皮细胞周期的变化。结果rhIL-11治疗和预防给药可通过促进小肠隐窝细胞增殖使肠损伤得到迅速修复。照射后小鼠小肠上皮细胞发生明显的G2期阻滞，rhIL-11治疗可明显提高S期细胞比例。结论rhIL-11对中子照射小鼠小肠损伤具有防护作用，并能够影响细胞周期的变化。     

rhIL-11对8.0Gy 60Co γ射线照射小鼠肠道损伤的防治作用研究

目的研究重组人白介素11(rhIL-11)对小鼠小肠上皮辐射损伤的防治作用。方法采用^60Coγ射线照射小鼠模型,观察rhIL-11照射前后给药对小鼠小肠上皮形态、隐窝细胞坏死和细胞增生的影响,用流式细胞仪检测小鼠小肠上皮细胞周期的变化。结果照射前给药对小肠隐窝辐射损伤有显著防护作用,照后给药具有促进恢复作用。照射后小肠上皮细胞发生明显的G2期阻滞,rhIL-11作用后使阻滞更明显并能提高S期细胞比例。结论rhIL-11对小鼠小肠辐射损伤具有明显的防护作用,可能与其对细胞周期的调控相关。     

ⅢB型前列腺炎患者治疗前后IL-8、IL-10及NGF的变化

目的：探讨ⅢB型前列腺炎患者治疗前后前列腺液（EPS）中白细胞介素-8（IL-8）、白细胞介素-10（IL-10）及神经生长因子（NGF）的变化和意义。方法：ELISA法检测20例前列腺正常男性及36例临床诊断为ⅢB型前列腺炎患者治疗前后EPS中IL-8、IL-10和NGF水平。结果：治疗前后患者EPS中IL-8、IL-10和NGF水平与正常组比较,有显著性差异。治疗后EPS中IL-8水平较治疗前水平下降,有显著差异。而IL-10和NGF水平与治疗前比较,差异不显著。结论：检测治疗前后前列腺液中IL-8、IL-10和NGF水平有助于了解ⅢB型前列腺炎患者治疗情况。     

重组人白细胞介素-11和姜黄素对中子照射致小鼠肠道损伤的治疗作用

Objective To explore the therapeutic effect of recombinant human interleukin(rhIL-11) and curcumin on jejunal damage in mice after neutron irradiation.Methods 140 male BALB/c mice were randomly divided into 4 groups:20 mice in healthy control group,60 mice in mere irradiation group,30 mice in IL-11 treatment group and 30 mice in curcumin treatment group.The mere irradiation group mice were wholly exposed to 3 Gy neutron irradiation.The treatment groups mice were intraperitoneally enterocoelia once a day for 5 d after irradiation.The mortality of the mice were observed.The mice in the control and mere irradiation groups were killed 6 h,1,3,and 6 d post-irradiation,respectively,and the mice of the 2 treatment groups were killed 3 and 6 d post-irradiation,respectively and the samples of jujunum were colleted.HE staining,argyrophilic of nucleaolar organizer regions staining,Feulgen staining,and image analysis were used to observe the pathology and levels of argyrophilic proteins and DNA.Results The mice in the mere irradiation group all died at 5 d post-irradiation,while 2 mice in the IL-11 treatment group and 3 in the curcumin group survived.Large area necrosis and exfoliation were found in the intestinal epithelial mucosa of the mere irradiated group mice since 6 h to 3 d after irradiation.Crypt cell regeneration was seen occasionally found 3 days later and much more 5 days later.Crypt cell regeneration was obviously found in the intestinal epithelial mucosa and lots of new villi were observed 5 d after irradiation in both treatment groups,however,the amounts of crypt cells and new villi of the curcumin treatment group were less than those of the IL-11 treatment group.The contents of AgNOR and DNA in the intestinal epithelial cells 5 days after irradiation of the 2 treatment groups were all significantly higher than those of the mere irradiation group (F = 0.015-0.035,all P ＜ 0.05) but without significant differences between them.Conclusions Jejunal damage in mice could be induced after 3 Gy neutron irradiation.rhIL-11 and curcumin might reduce the damage and promote the regeneration and repair of the intestinal epithelium.     

白细胞介素—11基因治疗促进放射损伤小鼠造血恢复的…

白细胞介素－１１（ＩＬ－１１）是一种新的造血生长因子，体内、外实验结果显示ＩＬ－１１具有显著的造血促进作用，它能作用于早期的造血干细胞及祖细胞，促进其增殖和分化。为了探讨ＩＬ－１１基因治疗放射损伤后造血恢复的促进作用，我们构建了含人ＩＬ－１１ｃＤＮＡ的逆转录病毒载体，并转染小鼠成纤维细胞系ＮＩＨ－３Ｔ３，经筛选获得了３株高表达ＩＬ－１１的转染细胞亚克隆，用高表达ＩＬ－１１的转染细胞作为载体细胞，进     

IL-11的体内外调控作用

ＩＬ 11是由骨髓基质细胞分泌的细胞因子。 1990年其ｃＤＮＡ克隆成功 ,1997年美国ＦＤＡ批准ｒｈＩＬ 11上市 ,成为第一个在临床上应用于肿瘤病人大剂量化、放疗后升高血小板的药物。近年来 ,随着对ＩＬ 11体内外调控作用及分子生物学研究的不断深入 ,人们认识到ＩＬ 11是一个多功能的细胞因子 ,具有广泛的生物学活性[1] 。1　对造血系统的调控作用1 1　对造血干 /祖细胞的调控　ＩＬ 11与ＩＬ 3、ＩＬ 4、ＩＬ 7、ＳＣＦ和ＧＭ ＣＳＦ等作用于早期或晚期造血的生长因子联用可刺激脐血、骨髓和外周血造血干 /祖细胞的分化和增殖 ,刺激ＣＦ…     

细胞因子白介素-6和白介素-10对中性粒细胞凋亡的影响

 目的观察白介素-6(IL-6)和白介素-10(IL-10)对离体健康人中性粒细胞凋亡的影响,了解它们在全身炎症反应综合征(Systemic inflammatory response syndrome,SIRS)和多器官功能障碍综合征(Multiple organ dysfunction syndrome,MODS)发病中的作用.方法选择20例健康志愿者,采取外周静脉血并分离中性粒细胞,每例分离的中性粒细胞平均分为4等份,分别给予生理盐水(对照组)、IL-6、IL-10、IL-6+IL-10,孵育24 h后,用AO/EB染色法计算每个样本中中性粒细胞的凋亡率、坏死率,并比较各组间凋亡率、坏死率的差异.结果与刘照组相比,IL-6组的中性粒细胞凋亡率显著降低(P＜0.01),L-10组中性粒细胞凋亡率则没有显著差异(P＞0.05);IL-10可对抗IL-6抑制中性粒细胞凋亡的作用(IL-6+IL-10组47.95±9.83 VS IL-6组35.80±8.59,P＜0.01).与对照组相比,IL-6组的中性粒细胞坏死率显著增加(P＜0.01),而IL-10组中性粒细胞坏死率则没有显著差异(P＞0.05).结论IL-6可抑制中性粒细胞的凋亡,增加中性粒细胞的坏死,促进中性粒细胞参与的炎症反应.IL-10不影响正常中性粒细胞的功能,但可抑制激活的中性粒细胞参与的炎症反应,具有一定的免疫调节作用.     

模拟150 m不安全快速上浮脱险致减压病大鼠肺组织白细胞介素-10和白细胞介素-13表达的变化

目的 研究模拟150 m不安全快速上浮脱险致减压病(decompression sickness,DCS)大鼠肺组织抗炎因子白细胞介素(interleukin,IL)-10、IL-13表达的变化规律.方法 模拟150 m不安全快速上浮脱险处理后0.5、3、6、12、24 h对大鼠肺组织IL-10、IL-13 mRNA表达水平及蛋白分子含量变化进行检测,并与常压空气对照组对比.结果 与对照组比较,模拟150m不安全快速上浮脱致DCS大鼠肺组织IL-10 mRNA水平在0.5h显著升高(2.104 4±0.361 5,P=0.026);IL-13 mRNA表达在0.5h(15.030 2±2.371 5,P=0.014)和3 h(2.459 8±0.419 1,P=0.018)显著增高.肺组织IL-10含量虽然在0.5h与常压空气对照组相比差异无统计学意义(P＞0.05),但其他各时间点均出现了不同程度的升高,且差异均有统计学意义(P=0.000);IL-13含量在0.5h和3h先降低,在6h和12 h再恢复接近正常水平,24h又降低,3h(P=0.028)、24 h(P =0.008)与常压空气对照组比较差异有统计学意义,6 h(P=0.041)、12 h(P =0.025)与24 h比较差异也具有统计学意义.结论 模拟150 m不安全快速上浮脱险致DCS大鼠肺损伤后,24 h内可导致肺组织IL-10 mRNA水平和IL-10、IL-13含量发生显著改变,具体机制有待进一步研究.     

IL—11对造血的刺激作用及其在辐射损伤治疗中的应用

体内外实验结果表明，IL－11（白细胞介素－11），可刺激骨髓巨核素，粒系和红系造血祖细胞的增殖，升高外周血小板，白细胞和红细胞数。因此，IL－11作为一种新的刺激骨髓造血细胞增殖的细胞因子具有它的特殊价值，可用于平时辐射事故病人和核战时伤员的救治，也可用于癌症患放，化疗后造血功能低下的治疗，具有广阔的临床应用前景。