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

Iglika Djoumerska-Alexieva 1 Lubka Roumenina 2 Anastas Pashov 1 Jordan Dimitrov 2, 1 Maya Hadzhieva 1 Sandro Lindig 3 Elisaveta Voynova 4 Petya Dimitrova 1 Nina Ivanovska 1 Clemens Bockmeyer 5 Zvetanka Stefanova 1 Catherine Fitting 6 Markus Bläss 3 Ralf Claus 3 Stephan Von Gunten 7 Srini Kaveri 2 Jean-Marc Cavaillon 6 Michael Bauer 3 Tchavdar Vassilev 3, 1
1 Institut Stephan Angeloff
2 CRC - Centre de Recherche des Cordeliers
3 Center for Sepsis Control & Care
4 NIAID - National Institute of Allergy and Infectious Diseases [Bethesda]
5 MHH - Hannover Medical School [Hannover]
6 Cytokines et Inflammation
7 Institute of Pharmacology
Abstract : 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.
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Molecular Medicine, Feinstein Institute for Medical Research, 2015, 21 (1), pp.1002-1010. 〈10.2119/molmed.2014.00224〉
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Iglika Djoumerska-Alexieva, Lubka Roumenina, Anastas Pashov, Jordan Dimitrov, Maya Hadzhieva, et al.. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes.. Molecular Medicine, Feinstein Institute for Medical Research, 2015, 21 (1), pp.1002-1010. 〈10.2119/molmed.2014.00224〉. 〈pasteur-01450975〉

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