Mels A K, Statius Muller M G, van Leeuwen P A, von Blomberg B M, Scheper R J, Cuesta M A, Beelen R H, Meijer S
Department of Surgery, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands.
Br J Surg. 2001 Apr;88(4):539-44. doi: 10.1046/j.1365-2168.2001.01722.x.
Surgery induces a postoperative immunosuppression, thereby possibly facilitating the outgrowth of pre-existing occult metastases or the seeding of disseminated tumour cells in patients with primary colorectal carcinoma operated on with curative intent. The hypothesis that adjuvant therapy with perioperative recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) would minimize postoperative immunosuppression was investigated in this pilot study.
Patients were allocated randomly to receive daily subcutaneous injections with either saline (n = 8) or rhGM-CSF 2.8 microg per kg body-weight (n = 8) from 3 days before operation until 4 days afterwards. Phytohaemagglutinin (PHA) skin test reactivity, monocyte human leucocyte antigen (HLA) DR expression and the extent of the acute-phase response, by determination of white blood cell count and differentiation, plasma interleukin (IL) 6 levels and body temperature in the perioperative period, were examined.
rhGM-CSF treatment minimized postoperative suppression in PHA skin test reactivity and increased the numbers of neutrophils and monocytes while enhancing the expression of HLA-DR in the postoperative period. Additionally, both postoperative plasma IL-6 levels and the incidence of fever tended to be higher in the rhGM-CSF group.
In this pilot study, perioperative administration of low-dose rhGM-CSF stimulated certain immune functions that are normally depressed after operation. The implications for the antitumour responses directly after operation and the formation of liver metastases are currently under investigation.
手术会引发术后免疫抑制,从而可能促使原发性结肠癌患者术前已存在的隐匿性转移灶生长,或使播散的肿瘤细胞着床,这些患者接受的是根治性手术。在这项初步研究中,对围手术期应用重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)进行辅助治疗可将术后免疫抑制降至最低的假说进行了研究。
患者被随机分配,从术前3天至术后4天,每天接受皮下注射,一组注射生理盐水(n = 8),另一组注射每千克体重2.8微克的rhGM-CSF(n = 8)。通过测定围手术期白细胞计数及分类、血浆白细胞介素(IL)-6水平和体温,检查植物血凝素(PHA)皮肤试验反应性、单核细胞人类白细胞抗原(HLA)-DR表达以及急性期反应程度。
rhGM-CSF治疗使术后PHA皮肤试验反应性的抑制降至最低,增加了中性粒细胞和单核细胞数量,同时在术后增强了HLA-DR的表达。此外,rhGM-CSF组术后血浆IL-6水平和发热发生率均有升高趋势。
在这项初步研究中,围手术期给予低剂量rhGM-CSF可刺激某些通常在术后受到抑制的免疫功能。目前正在研究其对术后直接抗肿瘤反应及肝转移形成的影响。