Blood cell redistribution in the lung after administration of recombinant human granulocyte-macrophage colony-stimulating factor.
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.
Gatti
E
E
Dept of Clinical and Biological Sciences, University of Torino, Italy.
Scagliotti
G V
GV
Ferrari
G
G
Mutti
L
L
Pozzi
E
E
Stacchini
A
A
Fubini
L
L
Aglietta
M
M
D000368:Aged; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000096:biosynthesis / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor