A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice.
Interleukin 1 (IL-1) is an endogenously produced cytokine that mediates a variety of physiological effects that may be beneficial or deleterious to the host. C57Bl/6 mice treated intravenously with a recently characterized human recombinant receptor antagonist protein to IL-1 (IL-1ra) had improved survival when treated after a lethal Escherichia coli endotoxin (lipopolysaccharide [LPS]) challenge. IL-1ra was effective when treatment was initiated after LPS, and intravenous administration every 4 h for 24 h was required. Serum levels of tumor necrosis factor (TNF) activity after LPS and in vitro TNF cytotoxicity were not altered by treatment with IL-1ra. These experiments provide direct evidence that the lethal effects of LPS may be mediated through the action of IL-1 and that the IL-1ra can provide a new treatment strategy for disease processes mediated via this cytokine.
Alexander
H R
HR
Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Doherty
G M
GM
Buresh
C M
CM
Venzon
D J
DJ
Norton
J A
JA
D000818:Animals; D004731:Endotoxins / Q000097:blood / Q000633:toxicity*; D004926:Escherichia coli; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D011506:Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha