The Immunomodulatory Effects of Albumin In Vitro and In Vivo

Albumin appears to have proinflammatory effects in vitro. We hypothesized that albumin would induce a state of tolerance to subsequent administration of lipopolysaccharide (LPS) in vitro and in vivo. RAW264.7 and primary peritoneal macrophages were treated with increasing doses of bovine serum albumin (BSA) and harvested for NF-kappa B luciferase reporter assay or TNF-alpha ELISA. In separate experiments, RAW264.7 cells were preconditioned with 1mg/mL BSA for 18 h prior to LPS (10 mu g/mL) treatment and harvested for NF-kappa B luciferase reporter assay or TNF-alpha ELISA. Finally, C57Bl/6 mice were preconditioned with albumin via intraperitoneal administration 18 h prior to a lethal dose of LPS (60mg/kg body wt). Blood was collected at 6 h after LPS administration for TNF-alpha ELISA. Albumin produced a dose-dependent and TLR-4-dependent increase in NF-kappa B activation and TNF-alpha gene expression in vitro. Albumin preconditioning abrogated the LPS-mediated increase in NF-kappa B activation and TNF-a gene expression in vitro and in vivo. The clinical significance of these findings remains to be elucidated.