Hepatocyte growth factor and neutrophil elastase in idiopathic pulmonary fibrosis

It has been hypothesized that hepatocyte growth factor (HGF) may play an important role in regulating the growth of lung epithelium and in the regeneration of the lung as a paracrine or endocrine factor in idiopathic pulmonary fibrosis (IPF). Based on this background, serum HGF was measured in 31 IPF patients (21 male/10 female, median age 60 years). Fifteen age-matched normal non-smokers served as the control. Hepatocyte growth factor was measured by enzyme-linked immunosorbent assay with monoclonal and polyclonal antibodies against human HGF (Otsuka Assay Laboratories, Tokushima, Japan). Elastase: alpha 1-proteinase complex was also measured by enzyme-linked immunosorbent assay. No patients had significant liver or renal dysfunction. As a result, mean (standard error) serum HGF concentration of the patients with IPF was 0.384 (0.022) ng ml-1, which was significantly high compared to normal non-smokers [0.213 (0.012) ng ml-1, P < 0.001, 95% confidence interval was between 0.104 and 0.238]. Serum HGF values correlated strongly with the plasma elastase: alpha 1 proteinase inhibitor complex (R = 0.679, P < 0.001). Immunohistochemical staining of lung tissue with anti-human neutrophil elastase showed scattered immunopositive cells mainly in interstitium. Immunohistochemical staining with mouse anti-human HGF antibody showed that HGF was distributed to the lung epithelial cells in IPF lung specimens obtained by open lung biopsy. These results suggest that HGF may play an important role in the pathogenesis of IPF.