G-CSF and IL-8 but not GM-CSF correlate with severity of pulmonary neutrophilia in acute respiratory distress syndrome.
Activated neutrophils play a major role in the pathogenesis of acute respiratory distress syndrome (ARDS), and persistence of pulmonary neutrophilia is related to poor survival. Interleukin (IL)-8 is implicated in recruiting neutrophils to the lungs but it has been postulated that granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), which can promote the survival of neutrophils by delaying apoptosis, may prolong the inflammatory response. The aim of this study was to investigate the levels of GM-CSF and G-CSF in the lungs of patients with ARDS and determine their relationship relative to IL-8 with levels of neutrophils and clinical outcome. The lungs of 31 patients with ARDS were sampled by means of bronchoalveolar lavage (BAL) and assays of the three cytokines were conducted via enzyme-linked immunosorbent assay. GM-CSF, G-CSF and IL-8 were all increased in the patients compared to healthy controls but concentrations of GM-CSF were much lower than those of G-CSF and IL-8 (GM-CSF<G-CSF<IL-8). Levels of G-CSF and IL-8, but not GM-CSF, correlated strongly with each other (rS=0.86, p<0.001) and with BAL neutrophil counts, and only levels of G-CSF were significantly higher in nonsurvivors than survivors (p<0.05). This evidence indicates that granulocyte colony-stimulating factor as well as interleukin-8 plays a role in the mechanisms of pulmonary neutrophilia in acute respiratory distress syndrome, whereas the role of granulocyte-macrophage colony-stimulating factor remains unclear. The higher levels of granulocyte colony-stimulating factor in nonsurvivors, together with previous reports that recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor occasionally induce acute lung injury, emphasize that the role of these mediators in pathogenesis needs to be elucidated.
Aggarwal
A
A
Cell Biology Unit, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Baker
C S
CS
Evans
T W
TW
Haslam
P L
PL
D000293:Adolescent; D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology*; D018450:Disease Progression; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis*; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration; D012128:Respiratory Distress Syndrome / Q000150:complications*; D012720:Severity of Illness Index
D016209:Interleukin-8; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor