Innate Immune Responses to Danger Signals in Systemic Inflammatory Response Syndrome and Sepsis

Abstract

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 κB 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.

Silver Nanoparticles Interactions with the Immune System: Implications for Health and Disease

“…The innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms, in a non-specific manner (Castellheim et al, 2009). This means that cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system, does not confer long-lasting or protective immunity to the host.…”

The proteolytically stable peptidomimetic Pam-(Lys-βNSpe)6-NH2 selectively inhibits human neutrophil activation via formyl peptide receptor 2

“…4 The regression did not converge. 5 Inhibitory effect was found, but the IC 50 value was out of the tested range. Lau-(Lys-βNSpe) 6 -NH 2 0.18 (0.14-0.24) -5…”

“…However, excessive, unbalanced, or prolonged inflammation can be detrimental to the host. In the case of sepsis, the massive release of pro-inflammatory factors into the circulation causes tissue damage possibly leading to organ dysfunction and ultimately death [3][4][5]. Novel anti-infective therapies are urgently needed due to the fact that excessive and non-compliant use of antibiotics has selected for multidrug-resistant bacterial strains.…”

Francisella tularensis Suppresses the Proinflammatory Response of Endothelial Cells via the Endothelial Protein C Receptor

“…Endothelial cells play a critical role in the clearance of an infection. When activated by a pathogen, these cells upregulate expression of adhesion molecules and secrete various chemokines, events that culminate in recruitment of circulating leukocytes (54). Throughout the course of tularemia in mice, the majority of F. tularensis in the blood are extracellular and viable (20).…”