Human recombinant interleukin-1 alpha protection against the lethality of endotoxin and experimental sepsis in mice.
Human recombinant interleukin-1 alpha (IL-1) has a diverse range of physiological activities which may be beneficial or deleterious to the host. Pretreatment with doses of IL-1 has been shown to protect mice against a subsequent lethal bacterial injection; however, the protective effects of a single intravenous (iv) dose of IL-1 have not been well characterized. The current experiments were performed to determine the best dose, timing, and duration of action of a single iv dose of IL-1 against a subsequent lethal challenge with intraperitoneal endotoxin (LPS) or experimental sepsis induced by cecal ligation and puncture (CLP). Female C57B1/6 mice treated with iv IL-1 24 hr prior to 30 mg/kg LPS ip had improved survival compared to saline-treated controls (P less than 0.01). IL-1 was also protective when given 6 to 72 hr, but not 2 or 96 hr, prior to LPS. IL-1 protection against LPS lethality was similar to protection seen with an iv dose of tumor necrosis factor (TNF). After CLP, survival was improved with IL-1 versus saline pretreatment (P = 0.02). Unlike previous work with TNF, no toxicity or lethality was observed at any dose of IL-1 administered. A single iv dose of IL-1 protects against the lethality of LPS and CLP in mice. IL-1 may be a useful treatment strategy in patients at risk for the development of life-threatening sepsis.
Alexander
H R
HR
Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Doherty
G M
GM
Fraker
D L
DL
Block
M I
MI
Swedenborg
J E
JE
Norton
J A
JA
D000818:Animals; D001424:Bacterial Infections / Q000401:mortality*; D002432:Cecum; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004926:Escherichia coli; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011677:Punctures; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha