TRANSIENT CHANGES IN THE MONONUCLEAR PHAGOCYTE SYSTEM FOLLOWING ADMINISTRATION OF THE BLOOD SUBSTITUTE LIPOSOME-ENCAPSULATED HEMOGLOBIN

We have examined the effects of administration of the blood substitute , liposome-encapsulated haemoglobin (LEH), in the normovolaemic rat. T est groups included LEH, lyophilized EH, the liposome vehicle, unencap sulated haemoglobin and normal saline, which were injected into the ta il vein (n = 6; n = 3 for sham and saline groups). Administration of L EH (2.5 g phospholipid, 1.25 g haemoglobin/kg rat) was followed by blo od sampling at 2 h, 24 h, 1 wk and 2 wk. Blood samples were analysed f or alanine aminotransferase, aspartate aminotransferase, alkaline phos phatase, gamma-glutamyltransferase, total and indirect bilirubin, seru m creatinine, albumin, total protein, lipase, cholesterol, blood urea nitrogen, haematocrit, haemoglobin and differential white blood cell c ounts. Observed effects following injection were mild and transient, w ith baseline values recovered at 1 wk. Alanine aminotransferase increa sed moderately in the LEH group at 24 h to 601 +/- 143 IU/dl (P < 0.00 01), with a return to baseline at 1 wk. Aspartate aminotransferase sho wed a smaller increase from 46 +/- 5 to 162 +/- 40 at 24 h and also re turned to baseline at the 1 wk measurement (P < 0.001). The transient increase in serum transaminases was not observed for the lyophilized L EH group, Tissue sections showed accumulation of liposome groups in re sident macrophages of the liver and spleen. Incubation of an adherent population of human peripheral blood monocytes with LEH in culture did not elicit the production of the inflammatory cytokine, tumour necros is factor. Pre-incubation of monocytes with LEH prior to exposure to e ndotoxin did, however, result in a reduced expression of this inflamma tory cytokine.