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.

Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n¼5609) born at mean (standard deviation [SD]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO 2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]¼1.16; 95% confidence interval [CI], 1.04e1.28

Sepsis is a severe infection-induced systemic inflammatory syndrome. Inhibition of downstream inflammatory mediators of sepsis, e.g., TNF-alpha, has failed in clinical trials. The aim of this study was to investigate the effects of inhibiting CD14, a key upstream innate immunity molecule, on the early inflammatory and hemostatic responses in a pig model of gram-negative sepsis. The study comprised two arms, whole live Escherichia coli bacteria and E. coli lipopolysaccharide (LPS) (n=25 and n=9 animals, respectively). The animals were allocated into treatment (anti-CD14) and control (IgG isotype or saline) groups. Inflammatory, hemostatic, physiological, and microbiological parameters were measured. The proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IL-8, but not the anti-inflammatory cytokine IL-10, were efficiently inhibited by anti-CD14. Furthermore, anti-CD14 preserved the leukocyte count and significantly reduced granulocyte enzyme matrix metalloproteinase-9 release and expression of the granulocyte membrane activation molecule wCD11R3 (pig CD11b). The hemostatic markers thrombin-antithrombin III complexes and plasminogen activator inhibitor-1 were significantly attenuated. Anti-CD14 did not affect LPS or E. coli DNA levels. This study documents that CD14 inhibition efficiently attenuates the proinflammatory cytokine response and granulocyte activation and reverses the procoagulant state but does not interfere with LPS levels or bacterial counts in E. coli-induced sepsis.-Thorgersen, E. B., Hellerud, B. C., Nielsen, E. W., Barratt-Due, A., Fure, H., Lindstad, J. K., Pharo, A., Fosse, E., Tønnessen, T. I., Johansen, H. T., Castellheim, A., Mollnes, T. E. CD14 inhibition efficiently attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis in pigs.