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

Autor: Iglika K Djoumerska-Alexieva, Srini V. Kaveri, Elisaveta Voynova, Nina Ivanovska, Ralf A. Claus, Catherine Fitting, Tchavdar Vassilev, Jean-Marc Cavaillon, Jordan D. Dimitrov, Clemens L. Bockmeyer, Markus Bläss, Michael Bauer, Zvetanka Stefanova, Petya Dimitrova, Sandro Lindig, Stephan von Gunten, Maya Hadzhieva, Anastas Pashov, Lubka T. Roumenina
Přispěvatelé: BENEDIC, Bénédicte, Institut Stephan Angeloff, Réseau International des Instituts Pasteur (RIIP), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Sepsis Control & Care, Jena University Hospital, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Hannover Medical School [Hannover] (MHH), Cytokines et Inflammation, Institut Pasteur [Paris] (IP), Institute of Pharmacology, University of Bern, This work was supported by grants from the Bulgarian-Swiss Research Programme (BSRP IZEBZO_142967), the Bulgarian National Science Fund (DFNI B02/29), the Pasteur Institute (ACIP A07-2012), the NATO Science for Peace Program (SfP 982158), and the German Federal Ministry of Education and Research (BMBF, grant 01EO1002) and grant 03Z2J521 (Meta-ZIK), both to the Centre for Sepsis Control and Care. We thank D Himsel for technical assistance., Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Réseau International des Instituts Pasteur ( RIIP ) -Institut Stephan Angeloff, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), National Institute of Allergy and Infectious Diseases [Bethesda], National Institutes of Health ( NIH ), Hannover Medical School [Hannover] ( MHH )
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Molecular Medicine
Molecular Medicine, 2015, 21 (1), pp.1002-1010. ⟨10.2119/molmed.2014.00224⟩
Mol Med
Molecular Medicine, Feinstein Institute for Medical Research, 2015, 21 (1), pp.1002-1010. ⟨10.2119/molmed.2014.00224⟩
Molecular Medicine, Feinstein Institute for Medical Research, 2015, 21 (1), pp.1002-1010. 〈10.2119/molmed.2014.00224〉
ISSN: 1076-1551
1528-3658
Popis: International audience; Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single pro-inflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could well 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 pro-inflammatory molecules, complement components and endogenous "danger" signals. The improved survival in endotoxemia was associated with serum levels of pro-inflammatory 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.
Databáze: OpenAIRE
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