Sepsis and septic shock

Abstract

For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

“…Despite the successful supportive therapies and decreasing mortality [1], there is still a lack of targets for earlier treatment [2,3]. Owing to the severe inflammation, sepsis often causes tissue damage and organ dysfunction, which determine the presenting symptoms of sepsis [2].…”

SOCS1 is a negative regulator of metabolic reprogramming during sepsis

“…Activation of pathogen recognition receptors triggers sequential events that drive production of inflammatory mediators (e.g., TNF-α, IL-6, IL-1β, KC, and MIP-2), as well the as the synthesis of microbicidal molecules, such as proteins and lipids involved in the generation of reactive oxygen species and reactive nitrogen species (RNS) (2,43). Although the inflammatory response is required to control infection, when left unchecked, it can be harmful, driving tissue damage, organ failure, and death (43)(44)(45).…”

“…The recognition of different microbial components, such as pathogen-associated molecular patterns (PAMPs) and host-derived damage-associated molecular patterns (DAMPs), induces a number of signaling programs, culminating in the activation of transcription factors, such STATs, activator protein 1 (AP-1), and NF-κB, among others (2). Activation of these pathways results in production of proinflammatory cytokines, including IL-1β, TNF-α, and IL-6.…”

High mobility group box 1 as a biomarker in critically ill patients

“…Hypoxic, stressed, injured, or dying cells release DAMPs, or alarmins, to activate the immune system, promote inflammation, but also initiate tissue repair . These processes are presumed to be hyper‐activated in critical illness, where cell death, systemic inflammation, tissue hypoperfusion, and infection determine the clinical course in the ICU . HMGB1 is a blueprint of DAMPs, because it can be actively released by innate immune cells in response to exogenous bacterial products or endogenous inflammatory stimuli and can be passively released from damaged parenchymal cells .…”