Interleukin-1α prevention of the lethality of Escherichia coli peritonitis

Interleukin-1 (IL-1) is an inflammatory mediator with a variety of described physiologic functions. IL-1α 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-1α in a murine model of bacterial peritonitis, to examine the differential induction of cytokines in animals with and without IL-1α pretreatment, and to assess differences in histologic evidence of end organ damage. IL-1α (27 μg/kg iv) conferred a survival advantage to mice given a lethal challenge of live Escherichia coli (2 × 10⁸ 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-1α at 1 hr after bacterial inoculum also did not improve survival. Mice pretreated with IL-1α developed significantly lower peak serum levels of TNF-α 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-1α-pretreated mice had a less prolonged elevation of serum levels of IL-6. IL-1α-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-1α confers a significant protective effect when given within a limited time range. Treatment outside this interval has no apparent beneficial effect. IL-1 may be of clinical value in patients at risk of developing life-threatening sepsis.