Localization of insulin-like growth factor-I in lung tissues of patients with fibroproliferative acute respiratory distress syndrome

Insulin-like growth factor-I (IGIF-I) is elevated in human fibrotic lung diseases and in animal models of pulmonary fibrosis, implicating IGF-I in the pathogenesis of fibrotic lung disease. We questioned whether IGF-I protein levels were enhanced in filbroproliferative acute respiratory distress syndrome (FP-ARDS). Serial lung tissue sections from a biopsy database were immunohistochemically stained for IGIF-I, IGF-I receptor, CD68, a-smooth muscle actin, collagens I and III, and proliferating cell nuclear antigen. Our results show enhanced staining of IGF-I and IGIF-I receptor, collagens I and III, smooth muscle actin, CD68, and proliferating cell nuclear antigen in FP-ARDS compared with control lung sections. In FPARDS specimens, prominent staining of IGF-I and IGIF-I receptor was seen in alveolar and interstitial macrophages as well as in a variety of mesenchymal cells. There was a correlation between IGF-I staining and CD68-positive cells, suggesting macrophages as a potential source of the IGF-I protein present in lungs. IGIF-I also correlated with enhanced collagen 1, collagen III, and proliferating cell nuclear antigen immunoreactivity, suggesting that IGF-I may play a role in the extracellular matrix protein deposition and cellular proliferation seen in the lungs of individuals with FP-ARDS. Our results indicate that IGF-I is increased in FP-ARDS and may be an important mediator in the progression of acute lung injury to FP-ARDS.