The mechanisms of pulmonary repair in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are poorly known. Hepatocyte Growth Factor (HGF) and Keratinocyte Growth Factor (KGF) are key factors involved in alveolar epithelial repair, present in the bronchoalveolar lavage fluid (BALF) from patients with ALI/ARDS. The role of BALF mediators in their production remains to be determined. We evaluated the overall effect of BALF from 52 patients: (27 ventilated patients with ALI/ARDS, 10 ventilated patients without ALI, and 15 non-ventilated control patients) on HGF and KGF synthesis by lung fibroblasts. Fibroblasts were cultured in the presence of BALF. HGF and KGF protein secretion was measured by ELISA and mRNA expression was evaluated by quantitative real time RT-PCR. Only BALF from ALI/ARDS patients up-regulated both HGF and KGF mRNA expression and protein synthesis (+271% and + 146% for HGF and KGF respectively). BALF-induced HGF synthesis from ALI/ARDS patients was higher than that from ventilated patients w/o ALI (p<0.05). HGF secretion was correlated with BALF IL-1beta levels (rho=0.62, p<0.001) and BALF IL-1beta/IL-1Ra ratio (rho=0.54, p<0.007) in the ALI/ARDS group. An anti-IL-1beta antibody partially (>50%) inhibited the BALF-induced HGF and PGE(2) secretion whereas NS-398 (a specific COX-2 inhibitor) completely inhibited it. Anti-IL1beta antibodies as well as NS-398 reversed the COX-2 up-regulation induced by BALF. Therefore, IL-1beta is a main BALF mediator involved in HGF secretion which is mediated through a PGE(2)/COX-2 dependent mechanism. BALF mediators may participate in vivo in the production of HGF and KGF by lung fibroblasts during ALI/ARDS.