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ABSTRACT: The objective of this study was to systematically review and quantitatively synthesize all randomized controlled trials (RCTs) that have compared important outcomes in critically ill patients who received an administration of probiotics.
A systematic literature search of PubMed, Scopus, and the Cochrane Central Register of Controlled Trials was conducted using specific search terms. Eligible studies were RCTs that compared the effect of prebiotics, probiotics, or synbiotics administration with control on ICU and hospital mortality rates in critically ill adult patients. Weighted mean differences (WMDs), pooled ORs, and 95% CIs were calculated using the Mantel-Haenszel fixed- and random-effects models.
Thirteen trials with 1,439 patients were analyzed. Probiotics did not significantly reduce ICU (OR, 0.85; 95% CI, 0.63-1.15) or hospital (OR, 0.90; 95% CI, 0.65-1.23) mortality. By contrast, probiotics administration reduced the incidence of ICU-acquired pneumonia (OR, 0.58; 95% CI, 0.42-0.79) and was associated with a shorter stay in the ICU (WMD, -1.49 days; 95% CI, -2.12 to -0.87 days). Finally, probiotics use was not associated with a shorter duration of mechanical ventilation (WMD, -0.18 days; 95% CI, -1.72-1.36 days) or a shorter hospital length of stay (WMD, -0.45 days; 95% CI, -1.41-0.52 days).
The present meta-analysis suggests that the administration of probiotics did not significantly reduce ICU or hospital mortality rates but did reduce the incidence of ICU-acquired pneumonia and ICU length of stay.
Chest 03/2013; 143(3):646-55. · 5.25 Impact Factor
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ABSTRACT: The objective of this study was to determine the effects of a TREM (triggering receptor expressed on myeloid cells 1)-like transcript 1-derived peptide (LR12) administration during septic shock in pigs. Two hours after induction of a fecal peritonitis, anesthetized and mechanically ventilated adult male minipigs were randomized to receive LR12 (n = 6) or its vehicle alone (normal saline, n = 5). Two animals were operated and instrumented without the induction of peritonitis and served as controls (sham). Resuscitation was achieved using hydroxyethyl starch (up to 20 mL/kg) and norepinephrine infusion (up to 10 μg/kg per minute). Hemodynamic parameters were continuously recorded. Gas exchange, acid-base status, organ function, and plasma cytokines concentrations were evaluated at regular intervals until 24 h after the onset of peritonitis when animals were killed under anesthesia. Peritonitis induced profound hypotension, myocardial dysfunction, lactic acidosis, coagulation abnormalities, and multiple organ failure. These disorders were largely attenuated by LR12. In particular, cardiovascular failure was dampened as attested by a better mean arterial pressure, cardiac index, cardiac power index, and SvO2, despite lower norepinephrine requirements. LR12, a TREM-like transcript 1-derived peptide, exhibits salutary properties during septic shock in adult minipigs.
Shock (Augusta, Ga.) 02/2013; 39(2):176-82. · 2.87 Impact Factor
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Sébastien Gibot
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ABSTRACT: The origins of sepsis-induced hyperlactatemia are still imperfectly understood and probably multifactorial, resulting both from an increased production by various tissues through aerobic and anaerobic glycolysis, and from a decreased lactate clearance. In the previous issue of Critical Care, Michaeli and colleagues showed that lactate elevation during mild endotoxemia is due to an increased aerobic production that does not take place in the muscle; other tissues/cells may thus be important contributors.
Critical care (London, England) 09/2012; 16(5):151. · 4.61 Impact Factor
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ABSTRACT: To investigate the role of myeloid-derived suppressor cells (MDSCs) during sepsis in mice. MDSCs are a heterogeneous population of cells that expand during cancer, inflammation and infection. These cells, by their ability to suppress T lymphocyte proliferation, regulate immune responses during various diseases. Their role during microbial infections is scarcely known.
Septic shock was induced by caecal ligation and puncture in adult male BALB/c mice; sham-operated animals served as controls. Animals were killed under anaesthesia to harvest blood and organs.
Polymicrobial sepsis induced a progressive accumulation of MDSCs in spleens that were found to be enlarged in surviving mice. MDSCs harvested at day 10 after the onset of infection were highly responsive to LPS in terms of cytokines secretion, NF-kB activation, ROS production and arginase I activity, whereas early-appearing (day 3) MDSCs poorly responded to this stimulus. By contrast, both day 3 and day 10 MDSCs were able to inhibit T cell proliferation. Adoptive transfer of day 10 MDSCs to septic mice attenuated peritoneal cytokine production, increased bacterial clearance and dramatically improved survival rate.
These results provide new information on the role of MDSCs, suggesting a protective effect during sepsis. Pharmacologic agents known to promote the expansion of MDSCs should thus be further studied for sepsis treatment.
European Journal of Intensive Care Medicine 05/2012; 38(6):1040-9. · 5.17 Impact Factor
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Marc Derive,
Youcef Bouazza,
Nacira Sennoun,
Sandra Marchionni,
Laura Quigley,
Valance Washington,
Frédéric Massin,
Jean-Pierre Max,
Jill Ford,
Corentine Alauzet,
Bruno Levy,
Daniel W McVicar, Sébastien Gibot
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ABSTRACT: The triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role during the onset of sepsis by amplifying the host immune response. The TREM-like transcript-1 (TLT-1) belongs to the TREM family, is selectively expressed on activated platelets, and is known to facilitate platelet aggregation through binding to fibrinogen. In this study, we show that a soluble form of TLT-1 is implicated in the regulation of inflammation during sepsis by dampening leukocyte activation and modulating platelet-neutrophil crosstalk. A 17-aa sequence of the TLT-1 extracellular domain (LR17) is responsible for this activity through competition with the TREM-1 ligand. Whereas early or late LR17 treatment of septic mice improves survival, treml-1(-/-) animals are highly susceptible to polymicrobial infection. The present findings identify platelet-derived soluble TLT-1 as a potent endogenous regulator of sepsis-associated inflammation and open new therapeutic perspectives. We anticipate soluble TLT-1 to be important in regulating leukocyte activation during other noninfectious inflammatory disorders.
The Journal of Immunology 05/2012; 188(11):5585-92. · 5.79 Impact Factor
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Sébastien Gibot,
Marie C Béné,
Robin Noel,
Frédéric Massin,
Julien Guy,
Aurélie Cravoisy,
Damien Barraud,
Marcelo De Carvalho Bittencourt,
Jean-Pierre Quenot,
Pierre-Edouard Bollaert,
Gilbert Faure,
Pierre-Emmanuel Charles
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ABSTRACT: Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessment of infection in critically ill patients is often a challenge for clinicians. In this setting, simple biomarkers, especially when used in combination, could prove useful.
To determine the usefulness of combination biomarkers to diagnose sepsis.
Three hundred consecutive patients were enrolled to construct a biologic score that was next validated in an independent prospective cohort of 79 critically ill patients from another center.
Plasma concentrations of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and procalcitonin (PCT) were assayed, and the expression of the high-affinity immunoglobulin-Fc fragment receptor I (FcγRI) CD64 on neutrophils (polymorphonuclear [PMN] CD64 index) in flow cytometry was measured. A "bioscore" combining these biomarkers was constructed. Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others (P < 0.001 for the three markers). These biomarkers were all independent predictors of infection, the best receiver-operating characteristic curve being obtained for the PMN CD64 index. The performance of the bioscore, better than that of each individual biomarker, was externally confirmed in the validation cohort.
This prospective study, including inceptive and validation cohorts of unselected intensive care unit patients, demonstrates the high performance of a bioscore combining the PMN CD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient.
American Journal of Respiratory and Critical Care Medicine 04/2012; 186(1):65-71. · 11.08 Impact Factor
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ABSTRACT: The triggering receptor expressed on myeloid cells-1 (TREM-1) is an immunoreceptor whose role is to amplify the inflammatory response mediated by the engagement of Toll-like and NOD-like receptors. As the expression of TREM-1 is believed to be upregulated during infection, this protein has been studied as a sepsis biomarker. In the previous issue of Critical Care, Su and colleagues reported on the usefulness of urinary soluble TREM-1 in diagnosing sepsis and assessing its severity. Importantly, the authors describe, for the first time, that urinary soluble TREM-1 measurement is able to predict the development of sepsis-associated acute kidney injury (AKI). If these results were to be confirmed by larger studies, urinary soluble TREM-1 would possibly become a new biomarker for sepsis-associated AKI.
Critical care (London, England) 11/2011; 15(6):1013. · 4.61 Impact Factor
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ABSTRACT: Sepsis is a common cause of morbidity and mortality in intensive care units. There is no gold standard for diagnosing sepsis because clinical and laboratory signs are neither sensitive nor specific enough and microbiological studies often show negative results. The triggering receptor expressed on myeloid cell 1 (TREM-1) is a member of the immunoglobulin superfamily. Its expression is upregulated on phagocytic cells in the presence of bacteria or fungi. This article reports on the potential usefulness of the assessment of the soluble form of TREM-1 in biologic fluids in the diagnosis of infection.
Critical care clinics 04/2011; 27(2):265-79. · 1.72 Impact Factor
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ABSTRACT: Probiotics have been shown to be able to restore a non-pathogenic digestive flora, to prevent digestive colonization by pathogenic bacteria, and to modulate immunity. The aim of this study was to assess the effects of prophylactic probiotic administration in patients ventilated for up to 2 days.
This study was performed as a double-blind, concealed randomized, placebo-controlled trial in a French medical intensive care unit (ICU). Adult patients mechanically ventilated for a period of more than 48 h received enterally administered probiotics (Ergyphilus, 2 x 10(10) lactic acid bacteria, mostly Lactobacillus rhamnosus GG, once a day) or placebo until successful weaning.
A total of 167 patients were included. The two groups were comparable at baseline. The 28-day mortality rates were not different in the probiotic (25.3%) and placebo groups (23.7%). Mortality rates in ICU and at 90 days were also unaffected by the treatment. The incidence of ICU-acquired infections did not differ significantly except for that of catheter-related bloodstream infections that was lowered by probiotics. On a prespecified subgroup analysis, we found a reduction of the 28-day mortality among severe sepsis patients (total n = 101) treated with probiotics (n = 52) with an odds ratio (OR) for death at 0.38 (95% CI 0.16-0.93, p = 0.035). By contrast, probiotics were associated with a higher mortality rate in non-severe sepsis patients (OR 3.09, 95% CI 0.87-11.01, p = 0.08).
Although numerous uncertainties remain (type and the number of strains to use, delay and length of administration), and despite an acceptable safety profile, the daily prophylactic administration of probiotics cannot be encouraged in the critically ill patient.
European Journal of Intensive Care Medicine 09/2010; 36(9):1540-7. · 5.17 Impact Factor
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ABSTRACT: Although regulatory T lymphocytes (Tregs) have a pivotal role in preventing autoimmune diseases and limiting chronic inflammatory conditions, they may also block beneficial immune responses by preventing sterilizing immunity to certain pathogens.
To determine whether naturally occurring Treg cells have a role in inflammatory response and outcome during shock state we conducted an observational study in two adult ICUs from a university hospital. Within 12 hours of admission, peripheral whole blood was collected for the measurement of cytokines and determination of lymphocyte count. Sampling was repeated at day three, five and seven. Furthermore, an experimental septic shock was induced in adult Balb/c mice through caecal ligation and puncture.
Forty-three patients suffering from shock (26 septic, 17 non septic), and 7 healthy volunteers were included. The percentage of Tregs increased as early as 3 days after the onset of shock, while their absolute number remained lower than in healthy volunteers. A similar pattern of Tregs kinetics was found in infected and non infected patients. Though there was an inverse correlation between severity scores and Tregs percentage, the time course of Tregs was similar between survivors and non survivors. No relation between Tregs and cytokine concentration was found. In septic mice, although there was a rapid increase in Treg cells subset among splenocytes, antibody-induced depletion of Tregs before the onset of sepsis did not alter survival.
These data argue against a determinant role of Tregs in inflammatory response and outcome during shock states.
Critical care (London, England) 02/2010; 14(1):R19. · 4.61 Impact Factor
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ABSTRACT: The Triggering Receptor Expressed on Myeloid cells (TREM)-1 is a recently identified molecule involved in monocytic activation and inflammatory response. It belongs to a family related to Natural Killer cell-receptors and is expressed on neutrophils, mature monocytes and macrophages. The engagement of TREM-1 synergizes with several Toll Like Receptors (TLR) and/or NOD Like Receptors (NLR) activation in amplifying the inflammatory response mediated by microbial components or danger signals. The implication of TREM-1 during experimental models of acute or chronic inflammatory conditions, as well as during cancer, begins to understand. Furthermore, the modulation of the TREM-1 signaling pathway by the use of small synthetic peptides derived from its extracellular moiety confers interesting survival advantages during experimental murine septic shock and protects from organ damage during other inflammatory diseases. This review summarizes the recent advances on TREM-1 biology and highlights the promises of its therapeutic modulation.
Self/Nonself - Immune Recognition and Signaling 01/2010; 1(3):225-230.
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ABSTRACT: To determine whether an epinephrine-induced early increase in arterial lactate concentration can prognosticate the outcome during shock state, we conducted a retrospective study in a 16-bed medical intensive care unit of a teaching hospital in France. One hundred consecutive patients admitted because of a shock state irrespective of etiology and treated with epinephrine were included. Patients were not enrolled if they received epinephrine administration before intensive care unit admission. Sequential arterial lactate measurements were performed at the time of epinephrine infusion (H0) and 4 h later (H4) in which Deltalactate was defined as (100 x [arterial lactate(H4)-arterial lactate(H0)]/arterial lactate(H0)) and expressed as a percentage. Etiology of shock was septic (82%), cardiogenic (10%), or hemorrhagic (8%). Twenty-eight-day mortality rate was 72%. At admission, arterial lactate concentration was elevated (4.96 +/- 3.8 mmol/L) and was further increased upon epinephrine administration, reaching a peak at H4 (8.22 +/- 3.66). When patients were stratified according to their outcome, nonsurvivors displayed the same pattern as survivors, although with a significant upward shift in values (ANOVA, P = 0.0003). The Sequential Organ Failure Assessment score and Deltalactate were the only variables associated with the 28-day risk of death, with an odds ratio of 1.32 (95% confidence interval [CI], 1.06-1.65; P = 0.01) and 0.99 (95% CI, 0.99-0.99; P = 0.03), respectively, in multivariate analysis. At a value of 100%, Deltalactate predicted death, with a 71% sensitivity (95% CI, 51%-87%) and a 67% specificity (95% CI, 43%-85%). Kaplan-Meier survival analysis confirmed this finding, with a 52.4% death rate among patients with Deltalactate greater than 100 comparatively to 84.7% when Deltalactate was less than 100 (log-rank test, P = 0.0002). An adapted response (lactate production) to a pharmacological trigger (epinephrine) is associated with better prognosis during shock of various etiologies.
Shock (Augusta, Ga.) 12/2009; 34(1):4-9. · 2.87 Impact Factor
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European Journal of Intensive Care Medicine 11/2009; 36(3):555-6. · 5.17 Impact Factor
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Sébastien Gibot
European Journal of Intensive Care Medicine 07/2009; 35(9):1644; author reply 1645-6. · 5.17 Impact Factor
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ABSTRACT: The triggering receptor expressed on myeloid cells (TREM) 1, a receptor expressed on the surface of neutrophils and monocytes/macrophages, synergizes with the Toll-like receptors in amplifying the inflammatory response mediated by microbial components. Because the pathogenesis of severe blood loss-induced excessive inflammation and multiple organ failure implies leukocyte activation and bacterial translocation, we hypothesized that the TREM-1 pathway modulation would prove beneficial in this setting. Wistar rats were subjected to a 1-h period of hemorrhagic shock and then reperfused with shed blood and ringer lactate for 1 h. At the time of reperfusion, animals were administered with LP17 (a synthetic soluble TREM-1 decoy receptor), a control peptide, or a vehicle (isotonic sodium chloride solution). Plasma concentration of TNF-alpha, IL-6, and soluble TREM-1 were measured by enzyme-linked immunosorbent assay. Lung permeability was assessed by the weight-dry ratio and fluorescein isothiocyanate-labeled albumin lung-blood ratio. Organ dysfunction was appreciated by measuring plasma aspartate aminotransferase and urea concentrations. Bacterial translocation was estimated by blood, mesenteric lymph nodes, and spleens culture. Hemorrhagic shock associated with cardiovascular collapse, lactic acidosis, systemic inflammatory response, and organ dysfunction that was partly prevented by LP17 administration. Hemorrhagic shock induced a marked increase in lung permeability that was also prevented by TREM-1 modulation. Finally, LP17 improved survival. Thus, the early modulation of the TREM-1 pathway by means of a synthetic peptide may be useful during severe hemorrhagic shock in rats in preventing organ dysfunction and improving survival.
Shock (Augusta, Ga.) 04/2009; 32(6):633-7. · 2.87 Impact Factor
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ABSTRACT: To determine whether synovial expression of triggering receptor expressed on myeloid cells 1 (TREM-1) is upregulated in patients with distinct types of inflammatory or non-inflammatory arthritis.
Synovial fluid (SF) samples were analysed for levels of soluble TREM-1 (sTREM; n = 132), tumour necrosis factor alpha (TNFalpha, n = 78) and leucocyte TREM-1 messenger RNA (n = 48). Synovial tissue from four rheumatoid arthritis (RA) patients, two patients with Crohn's-associated arthritis, one patient with ankylosing spondylitis and one patient with osteoarthritis were examined for TREM-1 expression by immunohistology, and three of the RA samples were also analysed by Western blotting.
Synovial fluid sTREM-1 levels in septic arthritis and RA were similar to each other and were each greater than those in gouty arthritis, non-septic/non-RA inflammatory arthritis and non-inflammatory arthritis. Synovial fluid TNFalpha and sTREM-1 levels correlated with each other, and sTREM-1 and leucocyte TREM-1 mRNA levels each correlated with SF leucocyte counts. TREM-1 in RA was expressed in situ in synovial tissue by cells of myelomonocytic lineage but was not detectably expressed in control osteoarthritis synovial tissue.
Synovial TREM-1 expression is increased in septic arthritis and RA. In patients with acute inflammatory arthritis, elevated SF sTREM-1 levels may point the clinician to a diagnosis of septic arthritis or RA. In RA patients, targeting TREM-1 may have therapeutic benefits by reducing local proinflammatory cytokine and chemokine release.
Annals of the rheumatic diseases 01/2009; 68(11):1768-74. · 8.11 Impact Factor
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Intensive Care Medicine 10/2008; 34(12):2134-5. · 5.40 Impact Factor
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ABSTRACT: The triggering receptor expressed on myeloid cells (TREM)-1, a receptor expressed on the surface of neutrophils and monocytes/macrophages, synergizes with the Toll-like receptors in amplifying the inflammatory response mediated by microbial components. Because the pathogenesis of ischemia-reperfusion-induced gastrointestinal tissue injury and multiple organ failure implies leukocyte activation and bacterial translocation, we hypothesized that the TREM-1 pathway modulation would prove beneficial in this setting.
Animal study.
Research laboratory.
Adult male Wistar rats (250-300 g).
Rats were subjected to intestinal ischemia-reperfusion induced by occlusion of the superior mesenteric artery during 60 mins and reperfused for 180 mins. At the time of reperfusion, animals were administered with LP17 (a synthetic TREM-1 inhibitor), a control peptide, or a vehicle (normal saline). Plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and soluble TREM-1 were measured by enzyme-linked immunosorbent assay. Hepatic activation of the transcriptional factor nuclear factor-kappaB was assessed by electrophoretic mobility shift assay. Hepatic oxidant-antioxidant balance was estimated by measurement of lipid peroxidation and catalase activity. Ileal mucosal permeability was estimated by fluorescein dextran-4 clearance and bacterial translocation by mesenteric lymph nodes culture.
Ischemia-reperfusion was associated with cardiovascular collapse, lactic acidosis, and systemic and hepatic inflammatory response that were partly prevented by LP17 administration. Liver lipid peroxidation and catalase depletion were attenuated by LP17. Ischemia-reperfusion induced a marked increase in ileal mucosal permeability and an associated bacterial translocation that was also prevented by TREM-1 modulation. LP17 delayed mortality.
The modulation of the TREM-1 pathway by the means of a synthetic peptide may be useful during acute mesenteric ischemia.
Critical care medicine 03/2008; 36(2):504-10. · 6.37 Impact Factor
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ABSTRACT: To investigate plasma high-mobility group box 1 protein (HMGB1) concentration and its relationship with organ dysfunction and outcome in septic shock patients.
Prospective, noninterventional study. Medical adult intensive care unit at a university hospital in France.
42 critically ill patients with septic shock.
Arterial blood was drawn within 12 h of admission for the measurement of plasma HMGB1 concentration by ELISA. Repeated sampling was performed on days 3, 7, and 14.
Median HMGB1 concentration was 4.4 ng/ml (IQR 1.2-12.5) at admission, with no difference between survivors and nonsurvivors. A positive correlation was observed between HMGB1 and SOFA score and lactate, and procalcitonin concentrations. There was a progressive but statistically nonsignificant decline in HMGB1 concentration among the survivors, while nonsurvivors showed an increase in HMGB1 level between days 1 and 3. SOFA score and lactate and procalcitonin concentrations did not vary significantly between days 1 and 3. When measured on day 3, HMGB1 discriminated survivors from nonsurvivors with 66% sensitivity and 67% specificity, and concentration greater than 4 ng/ml was associated with an odds ratio of death of 5.5 (95% CI 1.3-23.6).
Intensive Care Medicine 09/2007; 33(8):1347-53. · 5.40 Impact Factor
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ABSTRACT: Triggering receptor expressed on myeloid (TREM)-1 is integral to the inflammatory response occurring during septic shock, although its precise function has yet to be determined. Here we show that in vivo silencing of TREM-1 using siRNA duplexes in a fecal peritonitis mouse model resulted in a blunted inflammatory response and increased mortality. This was associated with impaired bacterial clearance related to marked inhibition of the neutrophil oxidative burst. By contrast, TREM-1-silenced mice were highly resistant to a lethal endotoxin challenge, while partial silencing of TREM-1 in the bacterial peritonitis model produced a significant survival benefit. These data highlight the crucial role of the TREM-1 pathway in mounting an adequate inflammatory and cytotoxic response to polymicrobial sepsis, and both the therapeutic promise and potential risks of its modulation.
European Journal of Immunology 03/2007; 37(2):456-66. · 5.10 Impact Factor
