Contribution of anti-inflammatory/immune suppressive processes to the pathology of sepsis.
Sepsis is the leading cause of death in critically ill patients in the United States. It is associated with enormous expenditures within the health care system and despite substantial human, medical and fiscal resources directed at this clinical entity we have only had a modest effect on the septic patient's long-term survival. However, extensive studies over the last few decades have begun to reveal important pathophysiological processes around which a few promising therapeutic strategies with potential benefits may be derived. It is generally believed, that the body reacts to a septic challenge with an intense hyper-inflammatory response, designed to eliminate the underlying pathogen. However, along with and in response to the intense pro-inflammatory reaction, mechanisms fall into place to counter regulate (control) this initial response, typically resulting in a down regulation of the inflammatory response. This frequently results in dysfunction of various immunological conditions and may result in the inability to ward off the infection and consecutively lead to multiple organ dysfunction, multiple organ failure and death. It is the aberrant development of this anti-inflammatory/ immunosuppressive response, in which it is important to expand our understanding of pathological components to develop potential remedy. Upon this background this review aims to provide an overview on the pathophysiological mechanisms which initiate or maintain the down regulation of the immune response to a septic challenge and which might be a starting point for the development of therapeutic strategies.
Perl
Mario
M
Division of Surgical Research, Department of Surgery, RI Hospital, Brown University School of Medicine, Providence, RI 02903, USA.
Chung
Chun-Shiang
CS
Garber
Megan
M
Huang
Xin
X
Ayala
Alfred
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D060908:CTLA-4 Antigen; D015536:Down-Regulation; D006801:Humans; D007107:Immune System / Q000473:pathology; D007154:Immune System Diseases / Q000473:pathology; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D016328:NF-kappa B; D011453:Prostaglandins; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide