Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock (original) (raw)

Septic shock: Pathogenesis and treatment

Indian Journal of Pediatrics, 1993

Septic shock is the host’s inflammatory response to infection. There are multiple endogenous mediators responsible for the pathogenesis of septic shock. Cytokines, nitric oxide and prostaglandins are some of the major mediators. The term sepsis syndrome allows for an earlier diagnosis and treatment. Management of septic shock is focused in maintaining hemodynamic stability and an adequate oxygen delivery and utilization. Careful attention to each organ-system is of paramount importance to prevent complications and improve outcome. Experimental therapies to modulate the inflammatory response are promising.

Molecular mechanisms involved in the pathogenesis of septic shock

Archives of Medical Research, 2004

Pathogenesis of the development of sepsis is highly complex and has been the object of study for many years. The inflammatory phenomena underlying septic shock are described in this review, as well as the enzymes and genes involved in the cellular activation that precedes this condition. The most important molecular aspects are discussed, ranging from the cytokines involved and their respective transduction pathways to the cellular mechanisms related to accelerated catabolism and multi-organic failure. Ć 2004 IMSS.

Pathophysiologic mechanisms in septic shock

Laboratory Investigation a Journal of Technical Methods and Pathology, 2014

The systemic inflammatory response that occurs in the septic patient as a result of an infectious insult affects multiple organs and systems, causing numerous physiological derangements. Alterations in phagocytic, lymphocytic and endothelial cell function and immune regulation are evident, leading to heterogeneity in a host's response to a septic challenge. In addition, the normal hemostatic balance shifts toward a procoagulant state through alterations in tissue factor, antithrombin, protein C and the inhibition of fibinolysis, which can result in thrombus formation and paradoxical hemostatic failure. In an effort to diagnose sepsis and predict outcomes, biomarkers such as C-reactive protein, pro-calcitonin, pro-and anti-inflammatory cytokines have been investigated with varying results. Targeted therapies for sepsis, most notably Xigris (recombinant human activated protein C), have proven unsuccessful and treatment continues to remain reliant on source control, antibiotics and supportive interventions, specifically early goal-directed therapy. This brief review gives an overview of the immunopathologic and coagulopathic alterations that occur in sepsis, soluble inflammatory mediators as potential diagnostic and prognostic biomarkers, and the clinical management of the septic patient.

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

Clinical Microbiology Reviews, 2003

SUMMARY Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory...

Cellular activation mechanisms in septic shock

Frontiers in bioscience : a journal and virtual library, 1998

Septic shock is an increasingly important clinical condition, characterized by systemic hypotension, ischemia, and ultimately organ failure. In Gram negative infection, the bacterial cell wall component, lipopolysaccharide (endotoxin, LPS), has been strongly linked to the pathophysiological responses that result in septic shock. LPS is bound in plasma to a protein called LPS-binding protein (LBP), which facilitates the binding of LPS to a cell surface receptor, CD14. Binding to CD14 stimulates cell signaling mechanisms that result in the production of inflammatory cytokines. However, the events which follow LPS binding to CD14 and which lead to the production of cytokines remain unclear. It has recently become evident that a number of phosphorylation cascades including MAP kinase pathways and NF-kappaB activation pathway are initiated by exposure of cells to LPS. These cascades act at both the transcriptional and translational levels to regulate cytokine production. This review will...

Septic Shock in Humans

Annals of Internal Medicine, 1990

Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome.