Introduction: During the course of systemic inflammation, most of the immune cell types get activated to a certain degree as part of, or contributing to, the cascade of physiopathological events. Whether for some cells, classically phagocytes of the innate immune system, it is clear that direct sensing of pathogen-associated molecular patterns leads to activation initiating systemic inflammation, the picture is not so clear for natural killer (NK) cells. While NK cells have been shown to express toll-like receptors (TLR), the role of these receptors on NKs during systemic inflammation has not been directly addressed. Methods: To directly assess the role of TLR expression on NK cells we used an adoptive transfer model in which NKs purified from the spleens of WT, TLR4KO and TLR2/4DKO mice were transferred intravenously to RAG2-/γc-/-(devoid of T, B and NK cells). Five days after reconstitution the mice were challenged intraperitoneally with conventional or TLR-grade lipopolysaccharide (LPS). Immune cell activation and production of IFNγ by NK cells was determined after 6 hours by FACS analysis. Results: We observed no differences in reconstitution of the recipient mice with NK cells from different backgrounds suggesting no difference in trafficking and survival of the transferred cells. At 6 hours after LPS challenge, WT, TLR4KO or TLR2/4DKO NK cells recovered from the spleen and lungs of RAG2-/γc-/mice showed comparable levels of CD69 activation marker expression. Intracellular labeling for IFNγ in NK cells also revealed no significant differences. Conclusion: Whether there is a role for direct TLR signaling on NK cells remains the objective of further investigations; however, our data show that in the course of a systemic inflammatory process, like endotoxinemia, the expression of TLR2 and TLR4 by NK cells makes no difference in terms of their activation and secretion of IFNγ P2 Role of 6-hour, 12-hour, and 24-hour lactate clearance in mortality of severe sepsis and septic shock patients.

reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. carbon dioxide 30 [27][28][29][30][31][32][33][34][35] mmHg and median temperature 37.1 [36.8-37.3]°C. After removal of artefacts, the mean monitoring time was 22 h08 (8 h54). All patients had impaired cerebral autoregulation during their monitoring time. The mean IAR index was 17 (9.5) %. During H 0 H 6 and H 18 H 24 , the majority of our patients; respectively 53 and 71 % had an IAR index > 10 %. Conclusion According to our data, patients with septic shock had impaired cerebral autoregulation within the first 24 hours of their admission in the ICU. In our patients, we described a variability of distribution of impaired autoregulation according to time. ReferencesSchramm P, Klein KU, Falkenberg L, et al. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium. Crit Care 2012; 16: R181. Aries MJH, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit. Care Med. 2012.

Background Despite advances in diagnostic methods and antibiotic therapy, community-acquired pneumonia (CAP) is still a major cause of morbidity and mortality worldwide. Risk of CAP has been attributed to pathogen virulence, host susceptibility and epidemiologic factors. A significant number of patients with CAP develop severe complications, such as sepsis, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS) and less fatal conditions (pleuritis, empyema) and syndromes (acute respiratory failure (ARF)). The variable clinical presentation of CAP suggests a genetic predisposition. Materials and methods This study was conducted to establish the possible contribution of functional gene polymorphisms in the oxidative stress related genes to the development of community-acquired pneumonia (CAP) complications. CAP subjects (n = 350) were genotyped for 16 polymorphic variants in the genes of xenobiotics detoxification CYP1A1, AhR, GSTM1, GSTT1, ABCB1, redox-status SOD2, CAT, GCLC, and vascular homeostasis ACE, AGT, AGTR1, NOS3, MTHFR, VEGFa. Results The multilocus model which included six or more risk alleles in the CYP1A1, GCLC, AGT and AGTR1 genes was associated with pleuritis, empyema, acute respiratory distress syndrome (ARDS), all pulmonary complications together and acute respiratory failure. Genetically mediated correlation between clinical conditions in CAP patients is shown in Table 1. In silico analysis with Set Distiller mode identified N-acetylcysteine (P = 1.08E-08) and oxygen (P = 1.92E-06) as the best descriptors for the considered gene set. Acute infections of the airways are associated with oxidative stress, which enhances viscosity of bronchial mucus, reduces the mucociliary clearance rate and expedites lung disease aggravation and progression. N-acetylcysteine is a wellknown mucolytic and antioxidant drug, an indirect precursor of glutathione. Conclusions The results of the study indicate that pneumonia aggravation up to destructive intrapulmonary complications and ARDS is mediated by polymorphisms in oxidative stress-related genes. P3 A retrospective study evaluating the efficacy of identification and management of sepsis at a Western Cape Province district level hospital internal medicine department, in comparison to the guidelines stipulated in the Surviving Sepsis Campaign 2012

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Introduction: During the course of systemic inflammation, most of the immune cell types get activated to a certain degree as part of, or contributing to, the cascade of physiopathological events. Whether for some cells, classically phagocytes of the innate immune system, it is clear that direct sensing of pathogen-associated molecular patterns leads to activation initiating systemic inflammation, the picture is not so clear for natural killer (NK) cells. While NK cells have been shown to express toll-like receptors (TLR), the role of these receptors on NKs during systemic inflammation has not been directly addressed. Methods: To directly assess the role of TLR expression on NK cells we used an adoptive transfer model in which NKs purified from the spleens of WT, TLR4KO and TLR2/4DKO mice were transferred intravenously to RAG2-/γc-/-(devoid of T, B and NK cells). Five days after reconstitution the mice were challenged intraperitoneally with conventional or TLR-grade lipopolysaccharide (LPS). Immune cell activation and production of IFNγ by NK cells was determined after 6 hours by FACS analysis. Results: We observed no differences in reconstitution of the recipient mice with NK cells from different backgrounds suggesting no difference in trafficking and survival of the transferred cells. At 6 hours after LPS challenge, WT, TLR4KO or TLR2/4DKO NK cells recovered from the spleen and lungs of RAG2-/γc-/mice showed comparable levels of CD69 activation marker expression. Intracellular labeling for IFNγ in NK cells also revealed no significant differences. Conclusion: Whether there is a role for direct TLR signaling on NK cells remains the objective of further investigations; however, our data show that in the course of a systemic inflammatory process, like endotoxinemia, the expression of TLR2 and TLR4 by NK cells makes no difference in terms of their activation and secretion of IFNγ P2 Role of 6-hour, 12-hour, and 24-hour lactate clearance in mortality of severe sepsis and septic shock patients.