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Down-Regulation of the Immune Response

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Part of the book series: Molecular and Cellular Biology of Critical Care Medicine ((MCCM,volume 3))

Abstract

Today, despite the use of novel new antibiotics, aggressive surgical intervention, improved nutritional support as well as the application of a variety of novel anti-inflammatory therapies, sepsis and the subsequent development of multiple organ failure, remains the leading cause of morbidity and mortality in the surgical intensive care unit (1;2;25). While it could be argued that limitations in experimental design might in part be responsible for the failure of these clinical trails, several things are also clear with respect to limitations of these anti-inflammatory approaches. First, the reason for choosing to pursue many of these anti-inflammatory agents was based primarily on findings made with models which did not competently emulate the patho-physiological process leading to sepsis and/or multiple organ failure (6). Second, most of the studies done with animal models have utilized pretreatment approaches, which fail to take into account the nature of the evolving septic state. Third, evidence of a clear infectious let alone inflammatory stimulus is frequently absent (7) in the patient population defined as septic by the Bone et al (8) criteria or described as having multiple organ dysfunction (9; 10). This raises the possibility that the development of the septic state and/or multiple organ failure syndrome may not simply be the result of an infectious or pro-inflammatory process alone.

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Ayala, A., Chung, CS., Song, G.Y., Grutkoski, P.S., Simms, H.H. (2003). Down-Regulation of the Immune Response. In: Doughty, L.A., Linden, P. (eds) Immunology and Infectious Disease. Molecular and Cellular Biology of Critical Care Medicine, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0245-6_3

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