Effects of intravenous infusion of highly purified vitamin B2 on lipopolysaccharide-induced shock and bacterial infection in mice

We investigated the effect of an i.v. infusion of highly purified vitamin B-2 (riboflavin 5'-sodium phosphate: purity >97%) on lipopolysaccharide-induced shock and bacterial infection in mice. Six hours after lipopolysaccharide injection or 1 h after bacterial infection, vitamin B-2 or human activated protein C (APC) was administered by 6-h i.v. infusion. Vitamin B-2 at 10 mg/kg/6 h and up to 80 mg/kg/6 h significantly improved lipopolysaccharide-induced endotoxin shock. APC was also effective at low doses, but was deleterious at higher doses. Moreover, vitamin B-2 at 80 mg/kg/6 h significantly reduced the lethality of Escherichia coli and Staphylococcus aureus infection, whereas APC at up to 600 units/kg/6 h was ineffective. The i.v. infusion of vitamin B-2 reduced the elevations of proinflammatory cytokines and nitric oxide induced by lipopolysaccharide. These results suggest that i.v. infusion of vitamin B-2 represents a promising strategy for the treatment of sepsis and septic shock. (C) 2004 Elsevier B.V. All rights reserved.