Reversible depression of the reticuloendothelial system by liposomes

The effect of various doses of different types (reverse phase evaporation vesicles and small unilamellar vesicles) of intravenously injected liposomes on reticuloendothelial activity, as measured by the blood clearance rate of intravenously injected carbon, was investigated. Also the effect of pretreatment with reverse phase evaporation vesicles on blood clearance and tissue distribution of a second dose of similar vesicles was determined. For all concentrations used reverse phase evaporation vesicles caused reduction in reticuloendothelial activity at least up to 4 h after injection. 24 h after administration the rate of carbon clearance returned to the control level. On the contrary small unilamellar vesicles did not block reticuloendothelial activity. Pretreatment with reverse phase evaporation vesicles (250 μmol/kg) caused an increased blood level and a decreased hepatic uptake of a second dose of the vesicles, injected 1 h after the first dose. This seems to be due to a depression of reticuloendothelial activity and not to a depletion of opsonins. Pretreatment with small unilamellar vesicles (250 μmol/kg) had no significant influence on the tissue distribution of a second dose of vesicles. Our results clearly indicate that reverse phase evaporation vesicles cause a reversible depression of reticuloendothelial activity and this depression seems to be induced by a saturation of reticuloendothelial cells with liposomes.     

Effect of scarlet fever toxin on the phagocytic activity of the reticuloendothelial system

In normal rabbits and mice, one i.v. injection of scarlet fever toxin (ET) (30 000 STD per kg of rabbit weight or 20-g mouse) elicited a similar biphasic change in carbon clearance rate - early depression followed by a stimulating phase - as has been described for Gram-negative endotoxins. Prolonged depression without a subsequent stimulation phase was obtained in mice by raising the ET dose. The reasons of the discrepancy between these findings and those of Hanna and Watson (1965b) are discussed. Pyrogenic tolerance to ET is not accompanied by accelerated carbon clearance and is not impaired by RES blockade. A possible mechanism of ET tolerance is suggested.