Human Albumin Reduces Endothelial Dysfunction; Improves Survival in Mouse Model of Sepsis

Infusion of human serum albumin formulated at a 4% concentration significantly improved survival time in Swiss mice injected with lipopolysaccharide (LPS) endotoxin, while 20% human albumin and normal saline provided no protective benefit, according to French investigators. The 4% human albumin, but not the other solutions, also reduced LPS-induced renal dysfunction.

Separately, in human uterine vein endothelial cells exposed to both LPS and tumor necrosis factor-α in the presence or absence of 4% or 20% human albumin, the 4% product activated endothelial nitric oxide synthase and restored LPS-impaired flow-dependent endothelial dilation in mesenteric arteries. The 4% human albumin blunted LPS-tumor necrosis factor-αinduced oxidative and nitrosative stresses in endothelial cells and increased their glutathione levels, while the 20% albumin solution did not.

The investigators concluded that their data confirm a protective effect of 4% human serum albumin treatment measured both by survival in this sepsis model, and by reduced endothelial dysfunction through inhibition of inflammatory and oxidative stress pathways induced by endotoxins. Conversely, much higher concentrations of human albumin were detrimental, suggesting a dose-dependent effect.