SEPSIS SYNDROMES: UNDERSTANDING THE ROLE OF INNATE AND... : Shock (original) (raw)

Review Article: PDF Only

Department of Surgery, University of Florida College of Medicine, Gainesville, Florida 32610-0286

Received 9 Nov 2000; first review completed 21 Nov 2000; accepted in final form 22 Feb 2001

Address reprint requests to Lyle L. Moldawer, PhD, Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610-0286.

Supported in part by grant R37 GM-40586 from the National Institute of General Medical Sciences and grant P30 HL-08912 from the National Heart, Lung and Blood Institute, United States Public Health Service. A.O. was supported in part by a grant from the Swiss National Science Foundation.

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Abstract

An intact innate and acquired immune response are essential for defeating systemic microbial infections. Recognition molecules, inflammatory cells, and the cytokines they produce are the principal means for host tissues to recognize invading microbes and to initiate intercellular communication between the innate and acquired immune systems. However, activation of host innate immunity may also occur in the absence of microbial recognition, through expression of internal “danger” signals produced by tissue ischemia and necrosis. When activation of the innate immune system is severe enough, the host response itself can propel the patient into a systemic inflammatory response syndrome (SIRS), or even multiple system organ failure (MSOF) and shock. Although most patients survive the initial SIRS insult, these patients remain at increased risk of developing secondary or opportunistic infections because of the frequent onset of a compensatory anti-inflammatory response syndrome (CARS). The initial activation of the innate immune response often leads to macrophage deactivation, T-cell anergy, and the rapid apoptotic loss of lymphoid tissues, which all contribute to the development of this CARS syndrome and its associated morbidity and mortality. Initial efforts to treat the septic patient with anticytokine therapies directed at the SIRS response have been disappointing, and therapeutic efforts to modify the immune response during sepsis syndromes will require a more thorough understanding of the innate and acquired immune responses and the increased apoptosis in the lymphoid tissue.