Decreased serum level of tumor necrosis factor in animals treated with lipopolysaccharide and liposomes containing phosphatidylserine.

ABSTRACT

The rise in serum level of tumor necrosis factor (TNF), produced by lipopolysaccharide, has been measured in mice and rabbits treated with phospholipid liposomes. After 3 daily ip injection (mice) or 5 daily i.v. injections (rabbits) of 30 mg/kg of a phospholipid mixture enriched in phosphatidylserine, the action of lipopolysaccharide was 80-90% reduced. The phospholipid effect is dose dependent, requires a minimum of two daily injections before the administration of lipopolysaccharide, and is still manifest 2 days after the last phospholipid dose. Among individual purified phospholipids, phosphatidylserine and phosphatidylethanolamine were effective whereas phosphatidylinositol, phosphatidylglycerol, and phosphatidylcholine did not show significant activity. The data indicate that the parenteral administration of liposomes containing the aminophospholipids phosphatidylserine, and phosphatidylethanolamine is an efficient mode to reduce the endotoxin-induced production of TNF. As suggested by liposome pharmacokinetics, this effect may be related to phospholipid accumulation in the mononuclear phagocyte system of liver and spleen.