MULTIPLE RESPONSES TO ADMINISTRATION OF LIPOSOME-ENCAPSULATED HEMOGLOBIN (LEH) - EFFECTS ON HEMATOPOIESIS AND SERUM IL-6 LEVELS

Liposome-encapsulated hemoglobin (LEH) has been tested in animals as a n oxygen-carrying red cell substitute and has been shown to be benefic ial in the treatment of hemorrhagic shock. The effects of LEH on immun e responses have not been studied thoroughly in any well-controlled mo del. Using a murine model, we evaluated nephrotoxicity and hepatotoxic ity as well as immune function parameters following LEH administration . Following intravenous administration of LEH, 1) a serum spike of int erleukin-6 (IL-6) occurred in mice at 4-8 hours, with no elevation of IL-1, tumor necrosis factor (TNF), or interferon-gamma (IFN-gamma); 2) the serum liver function enzymes SCOT (AST, aspartate aminotransferas e) and SGPT (ALT, alanine aminotransferase) were elevated at 48 hours; 3) only a slight increase in serum antibody to bovine hemoglobin was observed; and 4) increased hematopoietic activity was observed in the spleen and bone marrow. The finding that only IL-6 but not the associa ted TNF, IL-1, or IFN-gamma is secreted in vivo following LEH administ ration is novel and may have significance in defining the mechanisms u nderlying specific adverse responses observed with LEH administration in animals.