Cytokine activation through sublethal hemorrhage is protective against early lethal endotoxic challenge.
OBJECTIVE
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.


METHODS
Prospective, randomized, controlled experimental trial.


METHODS
Male BALB/c mice and transgenic mice deficient in IL-1 converting enzyme.


METHODS
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.


METHODS
University of South Florida Core General Surgery Research Facility, Tampa.


METHODS
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.
Zervos
E E
EE
Department of Surgery, University of South Florida, Tampa, USA.
Norman
J G
JG
Denham
D W
DW
Carey
L C
LC
Livingston
D
D
Rosemurgy
A S
AS
D000818:Animals; D006470:Hemorrhage / Q000276:immunology* / Q000401:mortality; D007375:Interleukin-1 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis
D007375:Interleukin-1; D008070:Lipopolysaccharides