Human Granulocyte Colony-stimulating Factor Therapy Research Articles

Effects of recombinant human granulocyte-colony stimulating factor therapy on rat pulmonary hypertension and its influence on endothelial progenitor cells

Objective To investigate the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) therapy on pulmonary hypertension,and its influence on number and functions of circulating endothelial progenitor cells (EPCs) in rats.Methods Eight week old Sprague-Dawlay rats were randomized into model group,treatment group and control group (8 rats in each group).The rats in model group and treatment group were treated with single subcutaneous injection of 1％ monocrotaline (50 mg/kg) to induce pulmonary hypertension models,while the control group was treated with phosphate buffered saline.Five days later,the rats in treatment group were administrated with 50 μg/(kg· d) rhG-CSF for 3 days.On day 21,peripheral blood was collected from caudal vein in all groups,and the percentage of EPCs in 100 000 mononuclear cells was evaluated by flow cytometry.Right ventricular systolic pressure was assessed,and the pathological changes of lung tissue and pneumoangiogram were observed by HE staining.Meanwhile,peripheral mononuclear cells collected from caudal vein were separated and cultured in vitro for EPCs.The cell ffunctions as proliferation,adhesion and migration ability were assessed.ANOVA and LSD test were applied as statistical analysis methods.Results (1) The right ventricular systolic pressure of rats in model group was higher than that in the controls [(48.13 ± 2.85) mm Hg vs (27.88 ± 3.04) mm Hg,t=2.016,P＜0.01],the lesion of endothelial cells in pulmonary arteriolar was evident,and the vessel wall was thickened.The pulmonary artery pressure of rats in the treatment group [(30.38 ± 2.83) mm Hg] was lower than that in the model group and close to the level of control group (t=0.376,P＞0.05) with mild pulmonary pathological changes.(2) The percentage off peripheral blood EPCs in mononuclear cells in the model group was decreased as compared to the control group [(0.016±0.007) ％ vs (0.031±0.011) ％,t=2.617,P＜0.01].After administration ofrhG-CSF,the EPCs in treatment group [(0.042±0.013) ％] was increased evidently as compared to the model group (t=4.325,P＜0.01) and the control group (t =1.942,P＜0.05).(3) The proliferation,adhesive and migrated cells of EPCs in model group were 0.49 ± 0.04,(6.93 ± 1.47) cells/HPF and (7.22±1.53) cells/HPF,lower than those in control group [0.68±0.07,(11.05±1.73) cells/HPF and (12.58±2.15) cells/HPF] and treatment group [0.63±0.06,(12.35±1.82) cells/HPF and (12.97±2.84) cells/HPF],the differences were statistically significant(all P＜0.05).Conclusions rhG-CSF may be effective in treating pulmonary hypertension through up-regulating the number and function of circulating EPCs in rat model of pulmonary hypertension. Key words: Hypertension, pulmonary; Granulocyte colony stimulating factor; Stem cells; Endothelium, vascular; Rats

Recombinant human granulocyte colony-stimulating factor therapy for patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease type 1b

AbstractThe purpose of this study was to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease (GSD) type 1b. Thirteen patients with neutropenia and/or neutrophil dysfunction secondary to GSD type 1b were treated with rhG-CSF. The effects of therapy on neutrophil numbers and in vitro neutrophil function and on bone marrow cellularity and morphology were studied. The clinical status of the patients and the occurrence of adverse events associated with rhG-CSF use were monitored. Use of rhG-CSF therapy was associated with a significant increase in circulating neutrophil numbers (P < .01) and an improvement in neutrophil function as assessed in vitro. In addition, rhG-CSF therapy produced a significant increase in marrow cellularity and an increase in myeloid:erythroid (M:E) ratio, indicating stimulation of granulopoeisis. No adverse effects on marrow function were noted; in particular, no myelodysplasia or marrow exhaustion was seen. Use of rhG-CSF therapy was associated with objective and subjective improvements in infection-related morbidity. The therapy was well tolerated, although all patients developed splenomegaly, and 5 patients developed mild hypersplenism that did not require any specific treatment. rhG-CSF therapy is efficacious in the management of neutropenia and neutrophil dysfunction associated with GSD type 1b. Patients on this therapy need to be monitored for hypersplenism. Continued follow-up will be necessary to confirm long-term safety; however, no significant short-term toxicity was noted.

再生不良性貧血のＧ‐ＣＳＦ治療中に発症したＮｅｕｔｒｏｐｈｉｌｉｃ Ｄｅｒｍａｔｏｓｉｓ

15歳の女性, 再生不良性貧血でG-CSF投与後に下肢·躯幹に有痛性皮下硬結が出現するようになった。久留米大学医学部皮膚科初診時, 左大転子部に直径7cmの中心壊死傾向を示す扁平隆起性紫紅色結節が認められた。病理組織学的には真皮乳頭層から脂肪織にかけて血管炎を伴わない密な好中球の浸潤と核破壊像および赤血球の血管外漏出の所見を呈していた。皮疹はG-CSF投与後に白血球増多を伴って再発したこと, 同薬の投与量を減量することにより再発が認められなくなったことから, 自験例をG-CSF投与により誘発されたneutrophilic dermatosisと診断した。

Low-dose recombinant human granulocyte colony-stimulating factor therapy in children with symptomatic chronic idiopathic neutropenia

OBJECTIVES: To prospectively define the lowest possible doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) that would benefit selected children with chronic idiopathic neutropenia whose disease was severe enough to interfere appreciably with quality of life. STUDY DESIGN: The efficacy of low-dose rhG-CSF therapy was investigated in six children with symptomatic chronic idiopathic neutropenia. All patients received rhG-CSF, 5 μg/kg subcutaneously, as a single daily dose until an absolute neutrophil count (ANC) above 1.5 × 10 9/L was observed. The rhG-CSF dosage interval and amount were then increased and decreased, respectively, in an alternating fashion until the lowest rhG-CSF dose that would maintain the ANC above 1.0 × 10 9/L (1000/mm 3) was reached. RESULTS: Although the minimal dose requirements varied, all patients were able to maintain a mean ANC >1.0 × 10 9/L during a mean follow-up period of 14 months at doses ranging from 1.0 μg/kg once weekly to 5.0 μg/kg every other day. Administration of rhG-CSF resulted in resolution of all preexisting chronic infections, reduction in the frequency of new infectious episodes, and discontinuation of prophylactic antibiotics. In all patients the ANC decreased to pretreatment values when further reduction or discontinuation of rhG-CSF therapy was attempted. By identifying the minimal effective dose in each patient, we were able to reduce the treatment cost by a mean of 81% compared with daily dosage at 5 μg/kg. CONCLUSIONS: Recombinant human granulocyte colony-stimulating factor therapy at low doses (≤5 μg/kg) every 2 to 7 days to symptomatic children with chronic idiopathic neutropenia is effective and no more costly than supportive treatment with antibiotics. (J P EDIATR 1996;129:551-8)