Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor.
Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose-dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge.
Alexander
H R
HR
Surgical Metabolism Section, National Cancer Institute, Bethesda, Maryland 20892.
Wong
G G
GG
Doherty
G M
GM
Venzon
D J
DJ
Fraker
D L
DL
Norton
J A
JA
D000818:Animals; D004357:Drug Synergism; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000008:administration & dosage*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides / Q000633:toxicity*; D008222:Lymphokines / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008070:Lipopolysaccharides; D008222:Lymphokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha