Gatti E, Scagliotti G V, Ferrari G, Mutti L, Pozzi E, Stacchini A, Fubini L, Aglietta M
Dept of Clinical and Biological Sciences, University of Torino, Italy.
Eur Respir J. 1995 Sep;8(9):1566-71.
Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a haematopoietic growth factor, has been shown to stimulate in vitro the production of interleukins 1, 6 and 8 (IL-1, IL-6 and IL-8), tumour necrosis factor-alpha (TNF-alpha) and GM-CSF by polymorphonuclear cells (PMNs), alveolar macrophages (AMs), fibroblasts and endothelial cells of the lung, and the growth and differentiation of resident alveolar macrophages. The aim of this study was to establish whether recombinant GM-CSF (rhGM-CSF), administered subcutaneously at a dose of 5 micrograms.kg-1 for 3 days in five patients with unresectable non-small cell lung cancer before starting chemotherapy, induces an increase in the alveolar cell count, and whether these cellular lung variations may be related to increases in the above-mentioned cytokines. In the bronchoalveolar lavage fluid (BALF) total cell count, polymorphonuclear cells, neutrophils, and alveolar macrophages increased significantly in comparison with the baseline, and the extent of variation of the BAL cell count was considerably greater than that of the circulating leucocytes. The mean levels of all the cytokines increased, but a significant difference with respect to the basal condition was observed only for IL-6 and IL-8. After rhGM-CSF treatment, significant correlations were found between neutrophil counts and the levels of IL-6 and IL-8. In conclusion, rhGM-CSF administration induces a cellular expansion in the lung, and the neutrophil increase appears to be related to increased levels of IL-8.
粒细胞-巨噬细胞集落刺激因子(GM-CSF),除了作为一种造血生长因子外,还被证明可在体外刺激多形核细胞(PMN)、肺泡巨噬细胞(AM)、成纤维细胞和肺内皮细胞产生白细胞介素1、6和8(IL-1、IL-6和IL-8)、肿瘤坏死因子-α(TNF-α)以及GM-CSF,并促进驻留肺泡巨噬细胞的生长和分化。本研究的目的是确定在5例不可切除的非小细胞肺癌患者化疗前,皮下注射剂量为5微克·千克⁻¹的重组GM-CSF(rhGM-CSF)3天,是否会导致肺泡细胞计数增加,以及这些肺部细胞变化是否可能与上述细胞因子的增加有关。在支气管肺泡灌洗液(BALF)中,与基线相比,总细胞计数、多形核细胞、中性粒细胞和肺泡巨噬细胞显著增加,且BAL细胞计数的变化程度明显大于循环白细胞。所有细胞因子的平均水平均升高,但仅IL-6和IL-8与基础状态相比有显著差异。rhGM-CSF治疗后,中性粒细胞计数与IL-6和IL-8水平之间存在显著相关性。总之,rhGM-CSF给药可诱导肺部细胞扩张,中性粒细胞增加似乎与IL-8水平升高有关。