Inhibition of In Vitro Synthesis of the Second (C2) and Fourth (C4) Components of Complement in Guinea Pig Peritoneal Macrophages by a Soybean Oil Emulsion

Abstract

Summary: Recently a soybean oil emulsion (Intralipid) (IL) has been released in the United States for use as a parenteral nutrient. The study reported here was undertaken to determine the effect of ingestion of IL on the synthesis and secretion of the second (C2) and fourth (C4) components of complement by guinea pig peritoneal macrophages in vitro. Cells exposed to IL had extensive Oil Red 0-positive granular-appearing accumulations of neutral lipid within the cytoplasm. Control cells did not stain with Oil Red 0. Incubation of the cells with concentrations of IL from 2.3-37.5 mg/100 ml resulted in a significant decrease in the production of both C2 and C4, which could not be explained by variability between plates. The decrease in total C2 or C4 production by cells incubated with IL for 4 hr was similar to the decrease in production by cells incubated with IL for 48 hr. Several lines of evidence indicated that the decrease of C2 or C4 was the result of decreased synthesis of these proteins and not interference of IL with the detection of the proteins or their secretion from the cells. Exposure of the cells to IL at all concentrations caused reduction of the number of cells having pseudopodia and a rounding-up of the cells. IL did not affect the rate of detachment of the cells from the plates through the 48-hr incubation period or the ability of the cells to exclude trypan blue. Total protein synthesis and total lysozyme production by control and IL-treated cells was similar. Speculation: Biopsy and autopsy studies of patients who received IL have demonstrated the presence of a fat pigment for up to 5 years in macrophages throughout the reticuloendothelial system, suggesting that macrophages do not process IL efficiently. The effect of IL infusion on C synthesis or serum C levels has not been studied. Inasmuch as macrophages are the major site of synthesis of both C2 and C4, C synthesis may be affected in patients receiving IL. This may be of particular importance in small infants.