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 respir atory distress syndrome (ARDS), and persistence of pulmonary neutrophilia i s related to poor survival. Interleukin (IL)-8 is implicated in recruiting neutrophils to the lungs but it has been postulated that granulocyte-macrop hage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), which can promote the survival of neutrophils by delaying a poptosis, 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 neut rophils 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-l inked immunosorbent assay. GM-CSF, G-CSF and IL-8 were all increased in the patients compared to healt hy controls but concentrations of GM-CSP were much lower than those of G-CS P and IL-8 (GM-CSF<G-CSF<IL-8). Levels of G-CSP and IL-8, but not GM-CSE; c orrelated strongly with each other (rs=0.86, p<0.001) and with BAL neutroph il counts, and only levels of G-CSF were significantly higher in nonsurvivo rs 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 i n acute respiratory distress syndrome, whereas the role of granulocyte-macr ophage colony-stimulating factor remains unclear. The higher levels of gran ulocyte colony-stimulating factor in nonsurvivors, together with previous r eports that recombinant granulocyte colony-stimulating factor and granulocy te-macrophage colony-stimulating factor occasionally induce acute lung inju ry, emphasize that the role of these mediators in pathogenesis needs to be elucidated.