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November 1997

Cytokine Activation Through Sublethal Hemorrhage Is Protective Against Early Lethal Endotoxic Challenge

Arch Surg. 1997;132(11):1216-1221. doi:10.1001/archsurg.1997.01430350066011

Objectives:  To determine the immunologic consequences of nonlethal hemorrhage on subsequent exposure to lipopolysaccharide (LPS) and to determine the role of interleukin 1β (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.Arch Surg. 1997;132:1216-1221