Interleukin-1 alpha prevention of the lethality of Escherichia coli peritonitis.
Interleukin-1 (IL-1) is an inflammatory mediator with a variety of described physiologic functions. IL-1 alpha has been shown to confer a survival advantage to experimental animals when administered before a lethal bacterial challenge. The experiments reported here were performed to define the effective pretreatment interval of a single intravenous dose of IL-1 alpha in a murine model of bacterial peritonitis, to examine the differential induction of cytokines in animals with and without IL-1 alpha pretreatment, and to assess differences in histologic evidence of end organ damage. IL-1 alpha (27 micrograms/kg iv) conferred a survival advantage to mice given a lethal challenge of live Escherichia coli (2 x 10(8) CFU/mouse ip) when the pretreatment was given 2 to 24 hr before the bacterial inoculum. Longer pretreatment intervals were not significantly protective. Treatment with IL-1 alpha at 1 hr after bacterial inoculum also did not improve survival. Mice pretreated with IL-1 alpha developed significantly lower peak serum levels of TNF-alpha after E. coli injection than did control mice. Pretreated and control mice had similar peak serum levels of IL-6 after bacterial challenge; however, IL-1 alpha-pretreated mice had a less prolonged elevation of serum levels of IL-6. IL-1 alpha-pretreated animals were protected from the histologic evidence of end organ damage seen in control animals. Thus, in this model of E. coli peritonitis pretreatment with a single intravenous dose of IL-1 alpha confers a significant protective effect when given within a limited time range. Treatment outside this interval has no apparent beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Lange
J R
JR
Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Alexander
H R
HR
Merino
M J
MJ
Doherty
G M
GM
Norton
J A
JA
D000818:Animals; D004927:Escherichia coli Infections / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D007375:Interleukin-1 / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D010538:Peritonitis / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha