Interleukin 1 release by human monocytes treated with liposome-encapsulated lipopolysaccharide

Liposome therapy offers a unique method of delivering antifungals, antiprotozoans, and macrophage-activating factors directly to reticuloendothelial cells. Although liposomes are entering clinical trials, their effect on Il 1 synthesis and release has yet to be determined. The beneficial, as well as possible pathological, effects of liposome therapy may be due to IL 1 released by reticuloendothelial cells. This study examined the effects of multilamellar phospholipid vesicles on the synthesis and release of IL 1 from human peripheral blood monocytes. Liposomes consisting of phosphatidylcholine and phosphatidylserine in molar ratio of 7:3 did not stimulate IL 1 release, and did not diminish the level of IL 1 release when monocytes were subsequently stimulated with LPS or Staphylococcus aureus. Surprisingly, LPS encapsulated in liposomes failed to stimulate IL 1 release from monocytes. This defect was limited to the release of IL 1, because monocytes stimulated with liposomes containing LPS had control levels of intracellular (cytosolic) and membrane IL 1. By contrast, LPS associated with lyophilized liposomes induced the secretion of IL 1 and behaved similarly to free LPS. These findings indicate that LPS activation of monocytes may involve not only the synthesis of IL 1 but activation of the secretory mechanism for IL 1, and that these two events could be independent, that the density of LPS molecules at the surface of the liposome may influence the degree of monocyte activation as measured by intracellular IL 1 synthesis, membrane accumulation, and secretion into the medium, and that intracellular lipids may not interfere with the secretory mechanism, because liposomes made with phospholipids differing in acyl chain length or the headgroup behaved identically.