Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis.
The systemic immune response induced by non-infectious agents is called systemic inflammatory response syndrome (SIRS) and infection-induced systemic immune response is called sepsis. The host inflammatory response in SIRS and sepsis is similar and may lead to multiple organ dysfunction syndrome (MODS) and ultimately death. The mortality and morbidity in SIRS and sepsis (i.e. critical illness) remain high despite advances in diagnostic and organ supporting possibilities in intensive care units. In critical illness, the acute immune response is organized and executed by innate immunity influenced by the neuroendocrine system. This response starts with sensing of danger by pattern-recognition receptors on the immune competent cells and endothelium. The sensed danger signals, through specific signalling pathways, activate nuclear transcription factor kappaB and other transcription factors and gene regulatory systems which up-regulate the expression of pro-inflammatory mediators. The plasma cascades are also activated which together with the produced pro-inflammatory mediators stimulate further the production of inflammatory biomarkers. The acute inflammatory response underlies the pathophysiological mechanisms involved in the development of MODS. The inflammatory mediators directly affect organ function and cause a decline in remote organ function by mediating the production of nitric oxide leading to mitochondrial anergy and cytopathic hypoxia, a condition of cellular inability to use oxygen. Understanding the mechanisms of acute immune responses in critical illness is necessary for the development of urgently needed therapeutics. The aim of this review is to provide a description of the key components and mechanisms involved in the immune response in SIRS and sepsis.
Castellheim
A
A
Institute of Immunology, Rikshospitalet University Hospital and University of Oslo, Oslo, Norway. castellheim@msn.com
Brekke
O-L
OL
Espevik
T
T
Harboe
M
M
Mollnes
T E
TE
D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D018805:Sepsis / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*