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Protein prevents detrimental immune effects of bacterial sepsis

llowing toxin administration. In fact, when annexin 1 knockout mice were given small doses of human recombinant annexin 1 in the first 24 hours following LPS treatment, survival increased to 60%.

These results, obtained in the lab of Dr. Mauro Perretti, highlight the delicate balance between the "pro-inflammatory/detrimental vs. anti-inflammatory/protective phases" of the immune response. Dr Perretti explained, "For too long, we have ignored anti-inflammatory/counter-regulatory mediators and the impact they have on pathology outcome; studying the way our body controls responses to infections can allow the modeling of new therapeutics with lower side effects."

The importance of this work is underscored by the fact that bacterial sepsis ranked among the top ten causes of death in both adults and neonates in 2002 in the United States (Natl Vital Stat Rep 2005, 53:1-89). The patients at greatest risk of developing sepsis and SIRS are those with impaired immune systems. When such patients are unable to control the underlying bacterial infection, their immune systems overcompensate and trigger a dangerous cascade of tissue damage.

Thus, to prevent death from sepsis, physicians must not only control the bacterial infection but better control the detrimental effects of the immune system. Dr. Perretti's lab is further investigating these immune pathways: "The ultimate goal is to use these new targets (e.g., a receptor for a given anti-inflammatory mediator) to develop better and safer drugs." The data for annexin 1 provide a new direction for such therapeutics that delicately balances removal of bacterial toxins and damage to host tissues.


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Source:American Journal of Pathology


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