Hill A D, Redmond H P, Austin O M, Grace P A, Bouchier-Hayes D
Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin.
Br J Surg. 1993 Dec;80(12):1543-6. doi: 10.1002/bjs.1800801216.
The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on murine antitumour responses was examined. Sixty mice received Lewis lung carcinoma implants and were then randomized to receive GM-CSF 1 microgram/day, GM-CSF 0.5 microgram/day or saline for 10 days and studied with regard to tumour volume, carcass weight and food intake. Macrophage antitumour mechanisms including oxygen free radical production and nitric oxide release were studied in peritoneal macrophages after co-culture with GM-CSF in vitro and in vivo. GM-CSF 1 microgram/day decreased tumour growth after 5 days (mean(s.e.m.) 0.62(0.14) versus 1.24(0.19) cm3, P = 0.017). GM-CSF upregulated macrophage antitumour mechanisms by enhancing the in vivo production of superoxide radicals (mean(s.e.m.) 0.69(0.06) versus 0.45(0.10) nmol, P < 0.05) and nitric oxide (mean(s.e.m.) 48(3) versus 24(4) mumol, P < 0.01). GM-CSF functions through the enhancement of macrophage tumoricidal activity, suggesting a therapeutic potential for this cytokine in the tumour-bearing host.
研究了粒细胞-巨噬细胞集落刺激因子(GM-CSF)对小鼠抗肿瘤反应的影响。60只小鼠植入Lewis肺癌后,随机分为三组,分别接受1微克/天GM-CSF、0.5微克/天GM-CSF或生理盐水,持续10天,并对肿瘤体积、胴体重量和食物摄入量进行研究。在体外和体内将腹膜巨噬细胞与GM-CSF共培养后,研究巨噬细胞的抗肿瘤机制,包括氧自由基产生和一氧化氮释放。1微克/天GM-CSF在5天后可降低肿瘤生长(平均值(标准误)0.62(0.14)对1.24(0.19)cm³,P = 0.017)。GM-CSF通过增强体内超氧自由基(平均值(标准误)0.69(0.06)对0.45(0.10)nmol,P < 0.05)和一氧化氮(平均值(标准误)48(3)对24(4)μmol,P < 0.01)的产生来上调巨噬细胞抗肿瘤机制。GM-CSF通过增强巨噬细胞的杀肿瘤活性发挥作用,提示该细胞因子在荷瘤宿主中具有治疗潜力。