重组人粒细胞集落刺激因子对中性粒细胞及其表面分子表达的影响

目的了解重组人粒细胞集落刺激因子(rhG-CSF)的使用对健康人外周血中性粒细胞比例及其细胞黏附分子和趋化因子受体的影响。方法给健康人注射rhG-CSF前后,用流式细胞仪检测外周血中性粒细胞表面分子的表达。结果注射rhG-CSF前中性粒细胞在外周血白细胞中所占比例的中位数为60%,注射后为85%,注射前后有显著差异(P<0.01)。注射rhG-CSF前中性粒细胞CD62L、CD49d的表达率中位数分别为82.84%和23.03%,注射后分别为18.30%和43.70%。注射后分别降低和升高(P<0.01)。注射rhG-CSF前后外周血中性粒细胞CD44、整合素CD11 a表达率无显著变化(P>0.10)。结论注射rhG-CSF可使健康人中性粒细胞的比例升高,CD49d表达率升高,CD62L表达率下降。     

重组人粒细胞集落刺激因子在甲巯咪唑所致粒细胞缺乏症中的治疗作用探讨

对６例甲巯咪唑所致粒细胞缺乏症用ｒｈＧ－ＣＳＦ和抗生素等治疗，并与另６例非ｒｈＧ－ＣＳＦ治疗组比较，结果发现：ｒｈＧ－ＣＳＦ组未出现阶血症，粒细胞恢复时间平均为６．８±３．９天，明显短于非ｒｈＧ－ＣＳＦ组（１２．２±５．８天）。提示ｒｈＧ－ＣＳＦ治疗可促进粒细胞恢复，缩短病程，从而减少机体合并感染的机会，改善预后。     

重组人粒细胞集落刺激因子在老年急性白血病化疗中的应用

目的 观察重组人粒细胞集落刺激因子(recombinant human granulocyte colony stimulating factor,rhG-CSF)在老年急性白血病化疗中的辅助治疗作用.方法 老年急性白血病患者30例分为A,B组,A组12例于化疗同时给予rhG-CSF,B组18例于化疗结束后第1天开始给予rhG-CSF 150μg/次,1次/d,皮下注射,7d后改为150 μg/次,隔日1次,皮下注射,用药至中性粒细胞绝对值≥2.0×109/L或应用14d后停药.治疗过程中体温＞38℃持续48h、有明确体征或影像学证实为深部感染者,给予抗生素治疗.比较2组化疗后发热持续时间、粒细胞缺乏症持续时间以及深部感染发生率.结果 A,B组化疗后发热和中性粒细胞恢复时间及深部感染发生率比较差异无统计学意义(P＞0.05).结论 化疗同时和化疗后使用rhG-CSF均可降低老年急性白血病患者化疗后发热和粒细胞缺乏症的持续时间;对化疗前伴有白细胞或中性粒细胞减少症或上次化疗出现严重感染者,于化疗同时给予rhG-CSF治疗,有缩短化疗后发热和粒细胞减少症持续时间的趋势.     

重组人粒细胞集落刺激因子在甲巯咪唑所致粒细胞缺乏症中的治疗作用…

对６例甲巯咪唑所致粒细胞缺乏应用ｒｈＧ－ＣＳＦ和抗生素等治疗，并与另６例排ｒｈＧ－ＣＳＦ治疗组比较，结果发现：ｒｈＧ－ＣＳＦ组未出现败血症，粒细胞恢复时间平均为６．８±３．９天，明显短于非ｒｈＧ－ＣＳＦ组。提示ｒｈＧ－ＣＳＦ治疗可促进粒细胞恢复，缩短病程，从而减少机体合并感染的机会，改善预后。     

重组人粒细胞集落刺激因子治疗急性粒细胞缺乏症11例

目的：总结重组人粒细胞集落刺激因子治疗急性粒细胞缺乏症的疗效。方法：应用国产重组人粒细胞集落刺激因子治疗11例急性粒细胞缺乏症，观察疗效及安全性。结果：本组11例急性粒细胞缺乏症均合并严重感染，经治疗后均显效，有效率100％，感染治愈率90．9％，仅1例因故中途放弃治疗，无1例死亡。结论：重组人粒细胞集落刺激因子能有效提高急性粒细胞缺乏症病人的粒细胞水平，对及时控制感染有较好的疗效，安全性高。     

重组粒细胞集落刺激因子在再生障碍性贫血中的应用

目的 探讨重组人粒细胞集落刺激因子(rh G-CSF)对再生障碍性贫血治疗的可行性。方法 选取2012年6月至2013年12月收治的再生障碍性贫血患者51例,随机分为观察组26例和对照组25例。对照组采用常规综合疗法治疗,观察组在常规综合疗法的基础上加用rh G-CSF皮下注射(5μg/kg,qd),疗程3个月。结果 治疗后两组患者外周血白细胞计数(WBC)、血红蛋白(Hb)、血小板计数(PLT)均较治疗前升高,CD3+、CD4+、CD8+均较治疗前下降(P均<0.05);观察组各项指标改善均显著优于对照组(P均<0.05)。治疗后,两组患者粒系增生程度及巨核细胞个数均较治疗前明显增加(P均<0.05),且观察组各指标及骨髓增生活跃率均明显高于对照组(P均<0.05)。观察组感染发生率、感染次数及抗生素应用天数均较对照组明显减少(P均<0.05)。结论 综合疗法联合rh G-CSF能迅速提高再生障碍性贫血治疗疗效,减少感染发生率,促进患者造血功能恢复。     

重组人粒细胞集落刺激因子所致不良反应临床分析

目的了解重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor,rhGCSF)致不良反应的特点,为临床合理用药提供参考。方法选择我院应用rhG-CSF发生药物不良反应的32例及检索中国期刊全文数据库、中国生物医学文献数据库筛选出的rhG-CSF相关不良反应的文献35篇(44例)为研究对象,对患者的一般情况、用药剂量、注射部位及方式、不良反应出现时间及临床表现进行分析。结果我院32例均采用传统的上臂三角肌肌内注射法(26例)或腹部皮下注射法(6例),不良反应发生时间一般在用药后24 h内,不良反应症状较轻,停药或应用抗过敏药物数天后自行消失。而数据库检索出的44例药物储存方式不详,采用皮下注射方法 31例,静脉给药4例,9例不详;发生急性全身药物不良反应8例(死亡2例,休克1例),不同器官或系统严重损害19例,局部反应17例。结论 rhG-CSF为生物制剂,易发生不良反应,不同的注射方式和注射部位以及储运方式与不良反应程度相关,应引起临床警惕。     

重组人粒细胞集落刺激因子致骨痛病人的护理

重组人粒细胞集落刺激因子(rhG-CSF)是一种多肽链的细胞生长因子,可特异地调节粒系祖细胞的增殖与分化,并能增强成熟中性粒细胞的功能,对机体应激防御系统有重要意义。乳腺癌病人使用骨髓抑制性化疗药物,皮下注射rhG-CSF有助于预防中性粒细胞减少症的发生,减轻中性粒细胞减少的程度,缩短粒细胞缺乏症的持续时间,加速粒细胞数的恢复,从而减少合并感染发热的危险性。骨关节疼痛是rhG-CSF不良反应之一,     

人重组粒细胞集落刺激因子对大鼠脑出血周围区新生血管的影响

背景：研究表明人重组粒细胞集落刺激因子可动员内皮前体细胞，增加脑缺血区域新生血管生成。目的：观察人重组粒细胞集落刺激因子对大鼠脑出血周围区新生血管的影响。设计、时间及地点：随机分组设计的动物对照实验，于2006-03／11在泸州医学院中心实验室完成。材料：健康雄性SD大鼠72只，人重组粒细胞集落刺激凼子。方法：72只大鼠按随机数字表法分为3组，假手术组、脑出血组、治疗组，每组24只。断尾取自体血通过鼠脑立体定向仪注入鼠脑内制备脑出血模型，似于术组用生理盐水代替自体血。治疗组于制模后1h腹腔注射人重组粒细胞集落刺激因子60μg／kg。假于术组、脑出血组不做任何处理。主要观察指标：于6，12，24，48，72h，7d6个时间点检测血肿周围区CD34^＋血管的表达，母个时间点检测4只。利用内皮细胞的标志性抗原CD34变化了解微血管的生成情况，CD34抗原也越多，新生血管越多。结果：脑出血组CD34^＋血管数明显高于假手术组（P〈0．05）；治疗组CD34^＋血管数明显高于脑出血组（P〈0．05），且在72h增多明湿，与7d比较差异无显著性意义（P〉0.05），但与6，12，24，48h比较差异有显著性意义（P〈0．05）。结论：人重组粒细胞集落刺激因子能够促进脑出血后血肿周围新生血管生成。     

重组人粒细胞巨噬细胞集落刺激因子治疗烧伤后残余创面

目的:探讨局部应用重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)凝胶治疗烧伤后残余创面的安全性和有效性。方法:采用随机、双盲、安慰剂同体对照的研究方法,将120处烧伤后残余创面,随机分为试验组(n=60)和对照组(n=60)。试验组采用rhGM-CSF凝胶治疗,对照组采用空白基质安慰剂治疗,试验周期为21d。观察用药后不良反应和创面愈合时间,以及不同时相点的创面愈合率、总有效率。结果:用药后不良反应轻微。试验组创面平均愈合时间为12.6d(95%可信区间11.9～13.3d),较对照组(16.8d,95%可信区间16.1～17.5d)明显缩短(P<0.01)。用药6、12d后,试验组创面愈合率分别为(53±13)%、(91±12)%,均显著高于对照组[(36±11)%、(73±14)%,P<0.01];试验组总有效率(13.00%、91.67%)均显著高于对照组(1.67%、53.33%,P<0.05);试验组疗效明显优于对照组(P<0.01)。结论:局部应用rhGM-CSF凝胶能促进烧伤后残余创面愈合,并且具有较好的安全性。     

Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis

OBJECTIVE: To evaluate the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on immunoparalysis as defined by a sustained decrease of HLA-DR expression on monocytes in patients with severe sepsis. DESIGN: Prospective, non-randomised observational study. SETTING: Two anaesthesiological intensive care units of a university hospital. INTERVENTION: Administration of a daily dose of 5 micro g/kg rhGM-CSF over a period of 3 days. PATIENTS: Nine consecutive patients with severe sepsis and a documented HLA-DR expression on peripheral monocytes of less than 150 mean fluorescence intensity (MFI) over a period of at least 48 h prior to intervention. MEASUREMENTS AND RESULTS: Mean MFI was 69.4+/-13.2 24 h before and 56.7+/-8.2 on the day of the administration of 5 micro g/kg rhGM-CSF. Within 24 h a significant increase of HLA-DR expression to a mean of 327.7+/-78.8 MFI was observed in all patients. This increase was maintained on days 2-10. It was accompanied by a significant rise in white blood count. The ex vivo TNF-alpha production in whole blood after lipopolysaccharide (LPS)-stimulation increased significantly from a mean of 82+/-29.2 pg/ml to 793+/-546.8 pg/ml. Apart from febrile reactions in two patients, no side effects were recorded. No increases of pro-inflammatory markers (IL-6, C-reactive protein, LPS-binding protein, procalcitonin) were observed. SOFA values before and after rhGM-CSF did not differ significantly. The mortality rate was 33%. CONCLUSION: This preliminary study demonstrates that rhGM-CSF upregulates HLA-DR expression on monocytes in septic patients with multi-organ dysfunction. Moreover, with the concomitant increase of the ex vivo whole blood TNF-alpha response, this upregulation of a monocytic activation marker is paralleled by a functional recovery.     

Expression of chimeric granulocyte-macrophage colony-stimulating factor/interleukin 2 receptors in human cytotoxic T lymphocyte clones results in granulocyte-macrophage colony-stimulating factor-dependent growth.

Adoptive immunotherapy with ex vivo-expanded antigen-specific cytotoxic T lymphocytes (CTLs) has been shown to clear viral infections and eliminate tumors in murine models. Clinical trials have also reported promising data for the use of adoptive immunotherapy to treat cytomegalovirus (CMV) and Epstein-Barr viral (EBV) infections in bone marrow transplant recipients. For these indications, the need for ex vivo-expanded CTLs is often short lived, until the immune system is reconstituted by the donor transplant. In chronic disease settings, increased longevity of adoptively transferred CTLs and generation of memory will be necessary. The additional administration of helper functions normally supplied by antigen-specific T helper (Th) cells will probably be essential for long-term survival of adoptively transferred CTLs. Toward this goal of supplying helper functions, we transduced human CTLs with chimeric GM-CSFR/IL-2R receptors that deliver an IL-2 signal on binding GM-CSF. Clones expressing the chimeric receptors proliferated in response to GM-CSF. Stimulation with antigen induced GM-CSF production and resulted in an autocrine growth loop such that the CTL clones proliferated in the absence of exogenous cytokines. This type of genetic modification has potential for increasing the circulating half-life and, by extension, the efficacy of ex vivo-expanded CTLs.     

Adjuvant therapy with recombinant interleukin-3 and granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are important members of the system of hematopoietic growth factors which control blood formation. Recombinant human (rh) GM-CSF stimulates proliferation and differentiation of myeloid cells and enhances effectively the regeneration of granulocytes and monocytes after chemotherapy or bone marrow transplantation. RhIL-3 acts on multipotent progenitor cells and induces an increase of leukocytes, platelets and reticulocytes after in vivo application. Combination of rhIL-3 and rhGM-CSF exerts a highly synergistic action on several hematopoietic cell lineages in monkeys and patients. Sequential application of rhIL-3 (5 days) followed by rhGM-CSF (10 days) has equivalent effects on myelopoiesis and thrombopoiesis compared with the effects of 15 days' monotherapy with rhGM-CSF on myelopoiesis and of a 15 days' treatment with IL-3 on platelet production. This combination seems to be very potent to reduce risk of neutropenia-associated infection and thrombocytopenic bleeding in patients with hematopoietic failure.     

Immunomodulatory effects of human recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF): evidence of antitumour activity

Human recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) is traditionally used as supportive care for patients undergoing cytotoxic chemotherapy or haematopoietic cell progenitor mobilisation. Emerging evidence suggests rhuGM-CSF, through activity on monocytes and dendritic cells, acts as a potent modulator of immune responses and has the ability to recruit inflammatory cells and cytokines to local and systemic sites of infection. The immunomodulatory effects of rhuGM-CSF suggest the potential to enhance innate and acquired immune responses against tumour-related antigens. Enhancement of innate antitumour immunity, especially in the context of minimal residual disease, is of central importance and presents the potential for meaningful contributions to long-term disease survival. This article discusses the immunomodulatory effects of rhuGM-CSF in the context of single-agent therapy in solid tumours, as well as combination therapy in lymphoma. In addition, dendritic cell modulation with rhuGM-CSF in haematopoietic progenitor grafts and rhuGM-CSF-transduced tumour vaccines will be discussed.     

Human recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3 cause basophil histamine release.

Histamine-releasing factors (HRFs) have been shown to be released from a variety of human cells, including T lymphocytes and alveolar macrophages. We considered the possibility that known cytokines might possess such activity on human basophils and/or mast cells and therefore tested preparations of human recombinant IL 3, IL 4, IL 5, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upon a panel of basophil donors. IL 3 and GM-CSF possessed significant histamine-releasing activity in 8 of 10 and 12 of 14 subjects, respectively. In each instance, a dose response could be demonstrated. IL 4 and G-CSF had no such activity, whereas IL 5 had activity in only 2 of 14 donors tested. We conclude that IL 3 and GM-CSF represent two effective HRFs, and suggest that HRF, as isolated based upon histamine-releasing activity, is likely to be heterogeneous in terms of molecular identity. Whether previously described HRFs relate specifically to IL 3 or GM-CSF must await primary sequence analysis of HRF and/or studies with monospecific antisera.     

Differential effects of granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor on tumor necrosis factor and interleukin-1 production in human monocytes

Human peripheral blood monocytes (PBM) cultured in the presence of 100-5,000 u/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) for 24 hr secreted small quantities of tumor necrosis factor (TNF), but not interleukin-1 (IL-1). The activation of PBM to produce TNF was weak and could be blocked by polyclonal anti-GM-CSF anti-serum. Neither LPS nor IL-2 were synergistic with GM-CSF in the production of TNF or IL-1. IFN gamma alone did not induce either cytokine, but in the presence of GM-CSF it caused a synergistic (100-fold) increase in TNF but not IL-1 production. Macrophage colony-stimulating factor (M-CSF) alone or in combination with LPS, IFN gamma or IL-2 did not stimulate PBM to produce TNF or IL-1 in 24 hr culture.