title: Multiple responses to administration of liposome-encapsulated hemoglobin (LEH): Effects on hematopoiesis and serum IL-6 levels.
abstract: Liposome-encapsulated hemoglobin (LEH) has been tested in animals as an oxygen-carrying red cell substitute and has been shown to be beneficial in the treatment of hemorrhagic shock. The effects of LEH on immune responses have not been studied thoroughly in any well-controlled model. Using a murine model, we evaluated nephrotoxicity and hepatotoxicity as well as immune function parameters following LEH administration. Following intravenous administration of LEH, 1) a serum spike of interleukin-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 SGOT (AST, aspartate aminotransferase) 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 associated TNF, IL-1, or IFN-gamma is secreted in vivo following LEH administration is novel and may have significance in defining the mechanisms underlying specific adverse responses observed with LEH administration in animals.
authors.affiliation: Naval Medical Research Instuitute, Bethesda, MD, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Rollwagen
authors.forename: W C
authors.initials: WC
authors.lastname: Gafney
authors.forename: N D
authors.initials: ND
authors.lastname: Pacheco
authors.forename: T A
authors.initials: TA
authors.lastname: Davis
authors.forename: T M
authors.initials: TM
authors.lastname: Hickey
authors.forename: T B
authors.initials: TB
authors.lastname: Nielsen
authors.forename: A S
authors.initials: AS
authors.lastname: Rudolph
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000906:Antibodies / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006454:Hemoglobins / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000906:Antibodies; D001802:Blood Substitutes; D016207:Cytokines; D006454:Hemoglobins; D015850:Interleukin-6; D008081:Liposomes; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase