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

Area of Science:

• Immunology
• Sepsis research
• Trauma-hemorrhage

Background:

• Lipopolysaccharide (LPS) is a potent endotoxin causing high mortality.
• Interleukin-1 beta (IL-1) plays a critical role in the inflammatory response to LPS.
• The immunologic effects of prior nonlethal hemorrhage on subsequent LPS challenge are not fully understood.

Purpose of the Study:

• To investigate the immunologic consequences of nonlethal hemorrhage on subsequent LPS exposure.
• To elucidate the specific role of IL-1 in mediating the response to LPS with and without prior hemorrhage.

Main Methods:

• Prospective, randomized, controlled experimental trial in male BALB/c mice and IL-1 converting enzyme-deficient transgenic mice.
• Animals were subjected to hemorrhage, LPS challenge, or hemorrhage followed 24 hours later by LPS challenge.
• Mortality and serum IL-1 levels were assessed post-exposure.

Main Results:

• Hemorrhage alone resulted in 100% survival; LPS alone resulted in 95% mortality.
• Hemorrhage 24 hours prior to LPS challenge significantly increased survival (67%) compared to LPS alone (5%; P < .001).
• Pre-hemorrhaged mice showed lower serum IL-1 levels post-LPS challenge, and IL-1 deficient mice exhibited 95% survival.

Conclusions:

• Nonlethal hemorrhage attenuates the IL-1 response to early immunologic challenge.
• This early immune suppression following hemorrhage appears protective against LPS.
• The protective effect is supported by the near-complete immunity to LPS in mice lacking biologically active IL-1.