Enhanced production of IGF-I in the lungs of fibroproliferative ARDS patients.

Insulin-Like Growth Factor I (IGF-I) has been identified in the lungs of individuals with fibrotic lung diseases. In a previous retrospective study, we showed enhanced IGF-I immunoreactivity in individuals with fibroproliferative acute respiratory distress syndrome (FP-ARDS), but we were unable to determine if this correlation was causative. This study was undertaken to prospectively investigate whether IGF-I expression correlated with the fibroproliferative process and whether IGF-I was induced and made in the lungs.

Adenovirus-mediated gene transfer of hIGF-IB in mouse lungs induced prolonged inflammation but no fibroproliferation.

Pulmonary fibrosis (PF), the end stage of a variety of fibroproliferative lung diseases, is characterized by excessive lung mesenchymal cell activation and extracellular matrix deposition. Most PF is induced after repetitive or chronic lung inflammation; however, a significant portion of PF occurs without apparent inflammation. The mechanisms of fibroproliferation are poorly understood.

Mechanisms of human complement factor B induction in sepsis and inhibition by activated protein C.

To investigate the potential role of the local expression of alternative complement factor B (hBf) in human sepsis, we examined the induction of Bf gene expression in human peripheral blood monocytes (PBMCs) from patients with septic shock and the mechanisms of hBf gene regulation by tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and lipopolysaccharide (LPS) in human monocytes. PBMCs from septic shock patients showed increased hBf mRNA expression when compared with control patients. Costimulation with TNF-alpha and IFN-gamma or stimulation with LPS demonstrated a time- and dose-dependent induction of hBf mRNA expression in human PBMCs.