白介素11在血小板减少疾病中的临床应用

目的观察国产重组人白介素11(rhIL-11)在治疗血小板减少疾病中的疗效.方法将55例血液肿瘤患者分为AB,BA 两组进行自身交叉对照;特发性(难治性)血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)组入选15例;血液肿瘤患者每例均化疗2个疗程(28 d为1个疗程).A疗程化疗结束后24 h加rhIL-11,剂量为25 μg/(kg*d),皮下注射,于化疗结束后24 h开始连用14 d,B疗程化疗后不使用rhIL-11,作为空白对照;自化疗开始隔日查血常规1次,观察各疗程外周血小板计数变化.ITP患者皮下注射rhIL-11 25 μg/(kg*d),连用14 d.结果血液肿瘤组:A疗程用rhIL-11后外周血小板数均值、最高值均大于 B疗程,A、B两疗程血小板数在用药前后差异有显著意义(P<0.05).A疗程血小板数低于50×109/L 的持续天数、恢复至75×109/L以上需要天数均有不同程度缩短;ITP组:rhIL-11治疗后患者血小板数均值逐渐升高,至第15天达(99±27)×109/L,用药前后血小板数差值为(80±16)×109/L.结论 rhIL-11对难治性血小板减少性紫癜及血液肿瘤化疗导致血小板减少有一定疗效,可耐受性好.     

基因重组人白细胞介素-11治疗恶性肿瘤化疗所致血小板减少症的临床探讨

目的观察基因重组人白细胞介素-11(rhIL-11)治疗恶性肿瘤化疗所致血小板减少症的临床疗效及不良反应。方法本组51例患者随机分为治疗组(27例)和对照组(24例)。治疗组病例化疗后外周血血小板计数≤50×109/L时,给予rhIL-11 1.5 mg皮下注射,1/d,连续用药5~14 d,平均9.2 d;当外周血血小板升至≥100×109/L时停用rhIL-11观察血像。对照组病例仅以输注血小板及对症治疗为主。结果治疗组患者应用rhIL-11前后自身比较血小板计数最低值显著升高,差异有显著性(P<0.01);治疗组患者化疗后应用rhIL-11血小板计数最低值较对照组化疗后的最低值显著升高,差异也有显著性(P<0.01);治疗组应用白介素-11后血小板计数低于5.0×109/L的天数比对照组明显缩短,两者比较差异也有显著性(P<0.01)。共治疗27例恶性肿瘤化疗所致的血小板减少症,显效9例(33.3%),有效18例(66.7%)。结论在恶性肿瘤化疗所致的血小板减少症的治疗中,rhIL-11的升血小板作用显著、安全、经济实用。     

重组人白介素-11治疗化疗所致血小板减少症的疗效和机制

目的观察重组人白介素-11(rhIL-11)治疗化疗后血小板(PLT)减少的疗效和安全性,并探讨其作用机制。方法34例(76周期)化疗后PLT减少患者接受rhIL211治疗,25μg·kg-1·d-1,皮下注射,连用4～16d,或至PLT升高幅度≥50×109/L时停药。观察rhIL211的疗效及不良反应,以ELISA法检测用药前血清IL-11水平,以RT-PCR法检测单个核细胞表面IL-11受体α链mRNA(IL-11Rα)的表达,分析rhIL-11的疗效与血清IL-11水平及IL-11Rα表达的关系。结果第1和第2周期化疗前,PLT基础值分别为(135.0±54.3)×109/L和(259.4±64.5)×109/L;应用rhIL-11的天数分别为7～16d(中位时间12d)和4～10d(中位时间6d),第1和第2周期rhIL-11的应用天数相比,差异有统计学意义(P<0.05);化疗后PLT计数<50×109/L的持续天数分别为7～13d(中位时间10d)和3～8d(中位时间5d),第1和第2周期PLT降低的持续天数相比,差异有统计学意义(P<0.05)。有30个周期PLT计数最高值>300×109/L,PLT计数最高值出现在应用rhIL-11后第10～17天(中位时间14d)。用药前的血清IL-11水平与用药后PLT计数最高值呈负相关。主要不良反应为水肿、乏力、头晕头痛和肌肉、关节疼痛。结论rhIL-11治疗化疗引起的PLT减少安全有效,虽起效缓慢,但作用持久;检测用药前血清IL-11水平对预测rhIL-11     

重组人白细胞介素-11的Ⅱ期临床研究

目的：观察重组人白细胞介素-11(rhIL-11)促血小板增殖作用及其临床毒副反应。方法：采用随机自身对照方法，患者随机分入AB组或BA组，AB即第1周期化疗结束后使用rhIL—11(A周期)，第2周期化疗给药结束后观察为空白对照；BA组则相反，观察rhIL-11的疗效及毒副作用。结果：A周期的血小板(PLT)最高值及化疗序日21d的PLT值明显高于B周期，不良反应主要为头痛及头晕、骨骼及肌肉疼痛、乏力、发热，两组差异无显著意义。结论：rhIL-11能升高外周血小板水平，促进因骨髓抑制所致血小板减少的恢复，不良反应轻，值得进一步开发和研究。     

重组人血小板生成素预防吉西他滨化疗相关血小板减少症的临床观察

目的：观察重组人血小板生成素（rhTPO）对吉西他滨相关血小板减少症（CIT）的预防作用。方法选择采用含吉西他滨化疗方案治疗出现Ⅱ级及以上血小板减少的恶性肿瘤患者74例,随机分为预防性注射重组人血小板生成素组（rhTPO组）和预防性注射重组人白细胞介素-11组（rhIL-11组）,在化疗的d3、d5、d7、d9,对rhTPO组和rhIL-11组患者分别进行皮下注射rhTPO和rhIL-11治疗,观察两组患者血小板下降情况、血小板开始恢复时间、血小板输注次数、治疗延迟及不良反应情况。结果预防性治疗后,两组患者血小板下降程度均较本组治疗前有改善,且rhTPO组患者Ⅲ~Ⅳ级血小板下降比例较rhIL-11组患者减少（P﹤0.05）;rhTPO组患者血小板开始恢复时间明显较rhIL-11组提前（P﹤0.01）;rhTPO组患者d8延迟、下周期（d22）延迟及心律失常发生率均较rhIL-11组降低（P﹤0.05）。结论预防性应用rhTPO和rhIL-11对CIT有积极的预防作用,rhTPO的疗效优于rhIL-11,且不良反应较轻。     

重组人白细胞介素11预防和治疗血小板降低的临床研究报告

背景与目的:肿瘤化疗可引起血小板下降,有必要研制预防和治疗血小板减少的药物。本文主要观察重组人白细胞介素11(rhIL-11)预防和治疗化疗引起的血小板减少的疗效和毒性。方法:研究分两部分,第一部分主要观察rhIL-11能否预防化疗引起的血小板下降。109例癌症患者进入对照研究组,随机分AB和BA两组,每例患者均化疗2个疗程。A疗程化疗后加rhIL-11,B疗程化疗后不用rhIL-11治疗。rhIL-11剂量为:50μg·(kg·d)-1于化疗结束后24h开始,臀部皮下注射,连用14天或直到血小板从最低点恢复至>400×109/L。第二部分主要观察rhIL-11能否治疗化疗引起的血小板下降。41例化疗后血小板<50×109/L的患者直接进入开放研究组,IL-1150μg·(kg·d)-1,连用14天或至血小板>400×109/L。结果:对照研究组107例患者可评价疗效,A疗程化疗后全组血小板平均数量为(246.49±88.64)×109/L;B疗程化疗后全组血小板平均数量为(180.24±83.34)×109/L(P=0.000)。A疗程Ⅲ/Ⅳ级血小板减少发生率为6.5%(7/107),B疗程Ⅲ/Ⅳ级血小板减少发生率为14%(15/107)(P=0.04)。A疗程化疗后血小板最低值:(136.46±74.64)×109/L,B疗程化疗后血小板最低值为(107.77±61.33)×109/L(P=0.000)。A疗程化疗后血小板最高值(381.28±150.39)×109/L,B疗程化疗后血     

重组人白细胞介素-11治疗化疗所致血小板减少

[目的]观察重组人白细胞介素-11(rhIL-11)治疗恶性实体肿瘤患者化疗所致血小板减少的临床疗效与毒副作用.[方法]38例第1周期化疗后血小板减少的恶性肿瘤患者随机分为治疗组和对照组,第2周期化疗后血小板计数≤75.0×109/L时,治疗组即给予皮下注射rhIL-11 25μg/(kg·d),连续用药至血小板≥100×109/L时停药,对照组不予rhIL-11,以对症治疗为主.同一患者2周期的化疗方案及剂量强度相同.[结果]第2周期化疗后与对照组比较,治疗组血小板降低幅度较对照组小,而且血小板≤75.0×109/L持续的天数也短,其差异均有统计学意义,P＜0.05.治疗组患者在进行自身比较中也发现,使用rhIL-11的第2周期血小板降低的幅度较前明显缩短,P＜0.05.不良反应均为Ⅰ～Ⅱ度,主要是疲劳、头晕、肌肉关节疼痛等.[结论]对恶性实体肿瘤化疗所致的血小板减少,重组人白细胞介素-11的治疗性给药方法效果确切,毒副作用轻,患者耐受性好.     

重组人白细胞介素-11治疗急性髓系白血病化疗后血小板减少36例

目的 观察重组人白细胞介素-11(rhIL-11,商品名:巨和粒)防治急性髓系白血病化疗后血小板减少的疗效及患者不良反应.方法 两组均采用DA或TA方案化疗,治疗组在化疗结束48 h后应用rhIL-11 3 mg/d皮下注射,连用10～14 d,观察两组化疗前后血小板计数、化疗后血小板最低值、血小板恢复时间及输注血小板的情况.结果 治疗组与对照组化疗前血小板计数差异无统计学意义(P＞0.05),治疗组血小板最低均值[(21.72±8.64)×109/L]高于对照组[(14.67±5.18)×109/L](P＜0.05),血小板恢复时间较对照组明显缩短[(10.43±2.38)d比(12.13±2.17)d]及输注血小板的数量显著减少[(1.50±1.08)个比(2.33±1.05)个](P＜0.05).结论 rhIL-11对治疗急性髓系白血病化疗后血小板减少有明显疗效,且患者不良反应轻微.     

重组人血小板生成素预防卵巢癌化疗相关血小板减少症的疗效和安全性

目的:比较使用重组人血小板生成素（rhTPO）与重组人白细胞介素-11（rhIL-11）预防卵巢癌化疗相关血小板减少症(CIT)的疗效和安全性。方法:入组II度以上卵巢癌CIT患者68例,随机分为预防性注射rhTPO治疗组（34例）和预防性注射rhIL-11治疗组（34例）,化疗后第一天、第二天用药。剂量:rhTPO 300 U/kg,rhIL-11 25~50 μg/kg。观察两组患者血小板下降情况、血小板开始恢复时间、血小板输注次数、治疗延迟及不良反应情况。结果:两组患者血小板下降程度均较本组预防性用药前有所改善,rhTPO组患者III-IV度血小板下降比例较rhIL-11组患者明显减少,使用rhTPO的促血小板增殖效果明显高于rhIL-11。rhTPO治疗组血小板开始恢复时间与血小板恢复至100×109/L以上所需要时间较rhIL-11治疗组明显缩短,统计学差异显著。rhIL-11治疗组有1例患者化疗后输入外源性血小板,rhTPO治疗组无患者输注血小板。应用rhTPO及rhIL-11对患者凝血功能无明显影响。与rhIL-11相比,rhTPO较少发生不良反应,患者耐受性较好。结论:既往化疗出现II度以上CIT的患者,预防性应用 rhTPO 和 rhIL-11 对CIT有积极的预防作用,rhTPO的疗效优于rhIL-11,并且具有良好的耐受性。     

重组人白细胞介素11治疗急性白血病化疗所致血小板减少的多中心研究

目的 探究重组人白细胞介素11(rhIL-11)治疗急性白血病化疗所致血小板减少症的效果及安全性.方法 纳入2016年2月至7月全国6个中心急性白血病化疗后血小板减少症[血小板计数(Plt)<50×109/L]患者,给予rhIL-11皮下注射治疗,2 mg/次,2次/d,连续使用7 d或至Plt经最低值后恢复到≥50×109/L时停用,观察受试者Plt恢复情况.结果 共入组患者112例,2例退出.110例有效病例中,rhIL-11治疗的总有效率为74.5％(82/110),治疗前后受试者Plt回升平均量为(70±54)×109/L,治疗有效者Plt恢复的平均时间为(8.7±3.0)d.在重度血小板减少症的治疗上,单药rhIL-11治疗与rhIL-11联合血小板输注治疗相比,受试者Plt恢复时间缩短,差异有统计学意义[(8.0±2.6)d比(9.6±3.5)d,t=2.17,P=0.03].结论 rhIL-112次/d皮下注射的给药方式可加速血小板恢复,降低血小板输注率,不良反应少,值得临床推广应用.     

Interleukin-11

Interleukin-11 (IL-11), a stromal cell-derived cytokine, has been known to act widely in hematopoietic and non-hematopoietic systems. IL-11 supports the growth of certain types of plasmacytoma and hybridoma cells, acts with interleukin-3 (IL-3) in shortening the Go period of early progenitors. IL-11 supports megakaryocyte colony formation and maturation, and acts as an autocrine growth factor in megakaryoblastic cell lines. In addition, IL-11 stimulates erythrocytopoiesis, enhances antigen-specific antibody responses, induces the synthesis of acute phase proteins, inhibits lipoprotein lipase activity and adipocyte differentiation, and promotes neuronal development. Administration of rhIL-11 to mice resulted in an increase of neutrophils and platelets. The human IL-11 gene is localized at 19q13.3-13.4, and codes 199 amino acids and 23 kDa with no N-glycosylation. Its receptor and signal transduction share partially those of interleukin-6 (IL-6). Further analysis of its role in normal and pathological state is necessary to determine the exact function and its application for clinical uses.     

Interleukin 11

IL-11 is a pleiotropic cytokine originally isolated from a bone marrow stromal cell line. It has been shown to share many activities with IL-6, namely to stimulate T cell-dependent B cell maturation, megakaryopoiesis and various stages of myeloid differentiation, but to inhibit adipogenesis. However, the activity of IL-11 on different stages of erythropoiesis in vitro clearly sets it apart form IL-6.

IL-11 has little hematopoietic colony stimulatory activity of its own although it sustains terminal differentiation of the late erythroid progenitors CFU-E. In combination with IL-3, IL-11 has profound stimulatory effects on early multipotent hematopoietic progenitors (pre-CFC_multi), on multilineage colony-forming cells (CFC_multi), as well as on erythroid progenitors. The combination of IL-11 with the ligand for c-kit (KL) preferentially acts on early cells since it promotes the multiplication of pre-CFC_multi and stimulates highly proliferative erythroid progenitors that yields remarkable macroscopic erythroblast colonies in culture. The synergistic activity of IL-11 and KL, two stromal factors present in the bone marrow microenvironment, points to a pivotal role of IL-11 in early hematopoiesis.

In vivo administration of recombinant human IL-11 elevates the number of circulating neutrophils and platelets and increased megakaryopoiesis in normal mice and primates.     

Phase I clinical study of CPT-11. Research group of CPT-11

CPT-11 is a new derivative of Camptothecin. Phase I clinical study of single administration with CPT-11 was carried out by a cooperative study group. Starting from 50 mg/m2 (n), dose was escalated to 350 mg/m2 (7n). Dose limiting factor was found to be a decrease in WBC counts (especially in neutrophils), and MTD was presumed to be 250 mg/m2 or more. Nadir of WBC counts was observed after about a week, and it took 2-3 weeks for recovery. The decrease in platelet number and hemoglobin content was mild. Other side effects included G-I toxicities, alopecia, etc. However, no toxic effects on the heart, kidney, lung were observed. SN-38, main metabolite of CPT-11, was observed in blood, and excreted rapidly. Anticancer effects were suggested with dose of 165 mg/m2 or more against colon cancer, gastric sarcoma, melanoma and lung cancer. It is suggested that the optimal dose schedule for an early Phase II study is 200 mg/m2 every 3-4 weeks. However, not only leukopenia but also marked G-I toxicities being noted in some cases, care should be taken for those side effects.     

Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells

Previous investigations have shown that interleukin-11 (IL-11) and the IL-11 receptor (IL-11R) have been correlated with the regulation of tumor progression, cellular growth and differentiation in several malignant tumors. The objectives of this study were to clarify the role of IL-11 and IL-11Ralpha in human gastric carcinoma. IL-11 and IL-11Ralpha were studied in 73 cases of surgically resected human gastric adenocarcinomas by immunohistochemistry. The invasive activity and cell signaling pathway of gastric carcinoma cell lines were also examined. Among the 73 cases of adenocarcinoma, 53 (72.6%) and 47 cases (64.4%) showed positive staining in carcinoma cells for the IL-11 and IL-11Ralpha proteins, respectively. Histologically, IL-11 expression correlated only with Lauren's classification (p<0.05). The expression of IL-11Ralpha correlated with the grade of tumor invasion (p<0.05) and vessel infiltration (p<0.01). All of the four gastric carcinoma cell lines expressed both IL-11 and IL-11Ralpha proteins in western blot analysis. Recombinant human IL-11 (rhIL-11) promoted the migration of SCH cells by the activation of the phosphatidylinositol-3 kinase pathway. Wortmannin diminished the promotion of chemotactic motility and invasive activity by rhIL-11. These findings suggest that the IL-11/IL-11R pathway plays an important role in the progression and the differentiation of human gastric carcinomas.     

重组人白细胞介素-11的Ⅱ期临床研究

[目的]观察国产注射用重组人白细胞介素-11（rhIL-11）促血小板生成的疗效及不良反应。[方法]采用随机双盲安慰剂自身交叉对照研究方法。[结果]rhIL-11使化疗后血小板最低值和化疗第21天血小板值．分别升高57．14％和103．9％，受试病人血小板低于正常值的持续天数明显短于安慰剂受试周期，P值均小于0．001。rhIL-11受试周期血小板平均值明显高于安慰剂受试周期。未发现严重不良反应。[结论]重组人白细胞介素-11能有效地促进血小板生成，临床使用安全。     

Experimental study on CPT-11 intraperitoneal chemotherapy--metabolism of CPT-11 in malignant ascites

The metabolism of CPT-11 in malignant ascites of gastric cancer patients with peritoneal seedings was studied in advance of the intraperitoneal chemotherapy of CPT-11 in humans. Malignant ascites and blood were drawn from gastric cancer patients. CPT-11 solution (20 mg/ml; 0.2 ml) was added into 3.8 ml ascites or plasma under 37 degrees C and CPT-11, SN-38 and SN-38GLU concentrations were measured with HPLC at times of 5, 30 and 60 minutes after addition of CPT-11. The change from CPT-11 to SN-38 was minimal not only in plasma, but also in malignant ascites. SN-38 GLU concentration was below the limit of measurement. This study showed that in malignant ascites, the enzymes such as carboxyesterase that convert CPT-11 to SN-38 were not present or minimal.     

白细胞介素-11的临床应用

白细胞介素-11是一种多效性细胞因子,能促进巨核细胞的分化和成熟,升高外周血小板数,保护胃肠道粘膜,调节机体的免疫功能,具有良好的临床应用前景.现综述有关白细胞介素-11临床应用的研究进展.