Iqbal Mohammad Perwaiz, Burney Ikram Ali
Department of Biological & Biomedical Sciences, Aga Khan University, Stadium Road, Karachi, Pakistan.
Department of Medicine, Sultan Qaboos University, Muscat, Oman.
Pak J Pharm Sci. 2014 Mar;27(2):245-8.
Low doses of granulocyte- colony stimulating factor (G-CSF) and granulocyte macrophage- colony stimulating factor (GM-CSF) have been shown to be beneficial in reducing duration of systemic antibiotic therapy and in-patient hospitalization by decreasing the period of neutropenia in cancer patients undergoing chemotherapy. Since the underlying mechanism is unclear, the aim of this study was to investigate whether the administration of G-CSF and GM-CSF in two different doses (low dose and standard dose) would result into resolution of neutropenia with concomitant increase in multiple forms of dihydrofolate reductase (DHFR, a pivotal enzyme in the pathway of de novo DNA synthesis). Thirty seven cancer patients (26 males and 11 females; age 14-73 years) having chemotherapy-induced neutropenia (absolute neutrophil counts <500/μl) were treated with colony stimulating factor (CSF) in the following manner: 11 received GM-CSF (7 received a dose 250 μg/m2 and 4 received a dose of 100 μg/m(2)); 26 received G-CSF (14 received a dose of 5 μg/kg and 12 received a dose of 2.5 μg/kg). CSFs was given every day till the absolute neutrophil count was more than 1,000/μl. Ten ml blood was collected from each patient and analyzed for total leukocyte count (TLC) and active DHFR and immunoreactive nonfunctional form of DHFR (IRE) in the cytoplasm of blood leukocytes by using methotrexate binding assay and enzyme-linked immunosorbent assay (ELISA). A significant increase (p<0.05) in concentrations of both active DHFR and IRE following stimulation with low as well as standard doses of CSFs was observed along with increase in the TLC. There was no significant difference in number of days to resolution of neutropenia at these two doses, indicating that even low doses of CSFs are clinically effective. Along with an increase in TLC, the levels of DHFR increased even at low doses of CSF suggesting that this might be one of the mechanisms for CSF-induced proliferation of leukocytes in neutropenic cancer patients.
低剂量的粒细胞集落刺激因子（G-CSF）和粒细胞巨噬细胞集落刺激因子（GM-CSF）已被证明有助于缩短全身抗生素治疗的持续时间，并通过减少接受化疗的癌症患者的中性粒细胞减少期来缩短住院时间。由于潜在机制尚不清楚，本研究的目的是调查给予两种不同剂量（低剂量和标准剂量）的G-CSF和GM-CSF是否会导致中性粒细胞减少症得到缓解，同时伴随多种形式的二氢叶酸还原酶（DHFR，从头合成DNA途径中的关键酶）增加。37例化疗引起的中性粒细胞减少症（绝对中性粒细胞计数<500/μl）的癌症患者（26例男性和11例女性；年龄14-73岁）接受了集落刺激因子（CSF）治疗，方式如下：11例接受GM-CSF（7例接受250μg/m²剂量，4例接受100μg/m²剂量）；26例接受G-CSF（14例接受5μg/kg剂量，12例接受2.5μg/kg剂量）。每天给予CSF，直到绝对中性粒细胞计数超过1000/μl。从每位患者采集10ml血液，通过甲氨蝶呤结合试验和酶联免疫吸附测定（ELISA）分析全白细胞计数（TLC）以及血液白细胞细胞质中活性DHFR和免疫反应性无功能形式的DHFR（IRE）。观察到低剂量和标准剂量的CSF刺激后，活性DHFR和IRE的浓度均显著增加（p<0.05），同时TLC也增加。这两种剂量下中性粒细胞减少症缓解天数无显著差异，表明即使低剂量的CSF在临床上也是有效的。随着TLC的增加，即使在低剂量的CSF下DHFR水平也会升高，这表明这可能是CSF诱导中性粒细胞减少症癌症患者白细胞增殖的机制之一。
