Acute respiratory distress syndrome alveolar fluid induces myofibroblast genes but suppresses keratinocyte growth factor in normal human lung fibroblasts.

Rationale Alveolar repair is critical to ARDS outcome. Myofibroblast induction is integral to healing by facilitating wound apposition (α-smooth muscle actin (α-SMA), secreting matrix (collagens 1 and 3), cytokines (TGF-β1 and connective tissue growth factor [CTGF]), and epithelial mitogens (keratinocyte growth factor [KGF]). We hypothesized that bronchoalveolar lavage fluid (BALF) from ARDS patients would induce multiple features of myofibroblasts. Methods ARDS BALF was collected within 48 hours of intubation. Patients with cardiogenic pulmonary edema were included as negative controls. ARDS and control BALF were incubated with normal human lung fibroblasts for 24 hours, and α-SMA, collagens 1 and 3, CTGF, TGF-β1, and KGF mRNA was measured by real-time RT-PCR. Results Ten ARDS patients and five negative controls were enrolled. The average age for ARDS patients was 53 ± 16 years. The average PaO 2 / FiO 2 ratio, compliance, and APACHE 2 scores were 118 ± 70, 21 ± 10, and 28 ± 8, respectively. ARDS BALF induced 110% more α-SMA ( p p p = .11) and 52% more collagen 3 ( p = .08) than controls. In contrast, control BALF induced 70% more KGF ( p r = −.78, p p p = .33). Conclusion Early ALI/ARDS BALF has predominant profibrotic characteristics and suppresses epithelial mitogen induction.