Dataset Information

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes.

ABSTRACT: Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as "genomic storm" in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous "danger" signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes.

SUBMITTER: Djoumerska-Alexieva I

PROVIDER: S-EPMC4982479 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes.

Djoumerska-Alexieva Iglika I Roumenina Lubka L Pashov Anastas A Dimitrov Jordan J Hadzhieva Maya M Lindig Sandro S Voynova Elisaveta E Dimitrova Petya P Dimitrova Petya P Ivanovska Nina N Bockmeyer Clemens C Stefanova Zvetanka Z Fitting Catherine C Bläss Markus M Claus Ralf R von Gunten Stephan S Kaveri Srini S Cavaillon Jean-Marc JM Bauer Michael M Vassilev Tchavdar T

Molecular medicine (Cambridge, Mass.) 20160331 1

Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as "genomic storm" in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin p ...[more]

PMID: 26701312

Similar Datasets

Project description:BackgroundSepsis is a life-threatening condition caused by severe infection. The efficacy of intravenous immunoglobulin (IVIG) as adjunctive therapy on mortality remains controversial. Moreover, IVIG may favorably affect sepsis-induced immunosuppression like persistent inflammation, immunosuppression, and catabolism syndrome (PICS).MethodsThis study was a retrospective cohort study using inpatient claims database provided by Medical Data Vision, which included approximately 190,000 episodes of intensive care unit admissions in Japanese acute care hospitals between April 2008 and September 2021. We used a propensity score-matched analysis to compare outcomes between the IVIG and control groups. Primary outcomes were 28-day mortality, while secondary outcomes included in-hospital mortality, the Barthel Index at discharge, length of hospital stay and laboratory data (albumin, C-reactive protein (CRP), and lymphocyte count) on days 14 and 28.ResultsOf the 17,626 patients enrolled, 15,159 (786 in the IVIG group and 14,373 in the control group) were included in the analysis. Propensity score matching generated 758 matched pairs. Before matching, 28-day mortality and in-hospital mortality were lower in the control group; however, in the matched cohort, 28-day mortality was significantly lower in the IVIG group than in the control group (90/758 [11.9%] vs 124/758 [16.4%]; risk difference [95% confidence intervals (CI)], -4.5% [-8.0% to -1.0%]; P = 0.015). In-hospital mortality in the matched cohort was also significantly more favorable in the IVIG group (137/758 [18.1%] vs 177/758 [23.4%]; risk difference [95%CI], -5.3% [-9.3% to -1.2%]; P = 0.013). Favorable outcomes in terms of albumin on days14 and 28 and CRP levels on day 28 were observed in the IVIG group.ConclusionsThe administration of IVIG was associated with a reduction in sepsis mortality and favorable outcomes in laboratory parameters and the functional status. These results will contribute to the ongoing debate on the efficacy of IVIG for sepsis. The results obtained herein suggest the benefit of IVIG, particularly in mitigating PICS. Further research, including prospective studies, is warranted to confirm these results and examine long-term outcomes.

Project description:Recent clinical trials indicate that probiotic administration in critical illness has potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of probiotic-mediated protection against infection and sepsis remain elusive. The authors evaluated the effects of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) on mortality, bacterial translocation, intestinal epithelial homeostasis, and inflammatory response in experimental model of septic peritonitis.Cecal ligation and puncture (n=14 per group) or sham laparotomy (n=8 per group) were performed on 3-week-old FVB/N weanling mice treated concomitantly with LGG, BL, or vehicle (orally gavaged). At 24 h, blood and colonic tissue were collected. In survival studies, mice were given probiotics every 24 h for 7 days (LGG, n=14; BL, n=10; or vehicle, n=13; shams, n=3 per group).Probiotics significantly improved mortality after sepsis (92 vs. 57% mortality for LGG and 92 vs. 50% mortality for BL; P=0.003). Bacteremia was markedly reduced in septic mice treated with either probiotic compared with vehicle treatment (4.39±0.56 vs. 1.07±1.54; P=0.0001 for LGG; vs. 2.70±1.89; P=0.016 for BL; data are expressed as mean±SD). Sepsis in untreated mice increased colonic apoptosis and reduced colonic proliferation. Probiotics significantly reduced markers of colonic apoptosis and returned colonic proliferation to sham levels. Probiotics led to significant reductions in systemic and colonic inflammatory cytokine expression versus septic animals. Our data suggest that involvement of the protein kinase B pathway (via AKT) and down-regulation of Toll-like receptor 2/Toll-like receptor 4 via MyD88 in the colon may play mechanistic roles in the observed probiotic benefits.Our data demonstrate that probiotic administration at initiation of sepsis can improve survival in pediatric experimental sepsis. The mechanism of this protection involves prevention of systemic bacteremia, perhaps via improved intestinal epithelial homeostasis, and attenuation of the local and systemic inflammatory responses.

Dataset Information

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes.

Publications

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets