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Cytokine activation through sublethal hemorrhage is protective against early lethal endotoxic challenge
E E Zervos1, J G Norman, D W Denham
1Department of Surgery, University of South Florida, Tampa, USA.
Objectives:
To determine the immunologic consequences of nonlethal hemorrhage on subsequent exposure to lipopolysaccharide (LPS) and to determine the role of interleukin 1 beta (IL-1) specifically in mediating the response to LPS with and without prior hemorrhage.
Design:
Prospective, randomized, controlled experimental trial.
Participants:
Male BALB/c mice and transgenic mice deficient in IL-1 converting enzyme.
Interventions:
Animals were subjected to hemorrhage (by cardiac puncture), LPS challenge by intraperitoneal injection, or hemorrhage followed 24 hours later by LPS challenge. Mortality was assessed every 4 hours for 96 hours following hemorrhage or LPS exposure. Serum IL-1 levels were determined 24 hours after exposure to hemorrhage and LPS.
Setting:
University of South Florida Core General Surgery Research Facility, Tampa.
Main Outcome Measures:
Mortality and serum IL-1 levels.
Results:
Hemorrhage alone resulted in complete survival, whereas LPS alone resulted in near-complete (95%) mortality. Hemorrhage, when given 24 hours before LPS challenge, afforded significant protection compared with LPS alone (67% survival vs 5% survival; P < .001). Serum IL-1 levels 24 hours after exposure to LPS were significantly lower in prehemorrhaged mice than in those receiving LPS alone. Transgenic mice incapable of producing biologically active IL-1 were further protected, demonstrating near-complete (95%) survival following hemorrhage and LPS challenge.
Conclusions:
Cytokine activation through nonlethal hemorrhage attenuates subsequent IL-1 response to early immunologic challenge. Such immune suppression appears to be protective early on and is supported by the near-complete immunity to LPS in animals incapable of producing biologically active IL-1.