Granulocyte-colony stimulating factor levels in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis.
BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) is known as a potent neutrophil chemotactic glycoprotein in vitro but its contribution to chemotactic activity in neutrophil mediated lung diseases is not yet known. The aims of this study were to determine whether G-CSF is present in high concentrations in bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis (IPF, also called cryptogenic fibrosing alveolitis), a neutrophil mediated lung disease, and to what extent G-CSF in BAL fluid contributes to neutrophil accumulation in the lung of patients with IPF. METHODS: G-CSF concentrations in BAL fluid samples from 16 healthy volunteers, 24 patients with IPF, and 73 patients with non-IPF lung disease were measured by enzyme linked immunosorbent assay. The relationship between G-CSF concentrations and neutrophil count in BAL fluid was also examined. Neutrophil chemotactic activity (NCA) was measured in BAL fluid in healthy volunteers and patients with IPF. The contribution of G-CSF to overall NCA in lungs with IPF was assessed by repeating the measurement of NCA after a complete neutralisation of G-CSF bioactivity by anti-human G-CSF antiserum. RESULTS: Detectable levels of G-CSF were found in BAL fluid of 83% of patients with IPF while the levels in all healthy volunteers were below the detection limit. In patients with IPF a significant correlation was observed between the BAL fluid neutrophil count and the concentration of G-CSF in the BAL fluid. The neutrophil count also correlated significantly with percentage forced vital capacity. In BAL fluid samples from patients with IPF the mean NCA value was reduced by 35% after neutralisation with an anti-human G-CSF antiserum. CONCLUSIONS: G-CSF may be involved in enhancing neutrophil accumulation in the lungs of patients with IPF.