Passive immunotherapy with
modified intravenous immunoglobulins (IVIg) improves survival in
experimental sepsis by attenuating inflammatory and coagulation pathways
-
1
Bulgarian Academy of Sciences, Bulgaria
T. Vassilev1, I. Djoumerska-Alexieva1, J. Dimitrov2, L. Roumenina2, E. Voynova1, I. Nina Ivanovska1, K. Srini2;
1Stefan Angelov Institute of Microbiology, Sofia, Bulgaria, 2INSERM Unit 872, Paris, France.
The exposure of some IgG antibodies to ferrous ions is known to enhance their polyspecificity that includes the ability to bind at least one pro-inflammatory cytokine (J.Biol.Chem.2006:281,439). Sepsis is a medical disaster that responds poorly to available drugs including intravenous immunoglobulin (IVIg) preparations. IVIg, pre-exposed in vitro to Fe(II) ions was used for passive immunotherapy of mice with sepsis induced by the injection of LPS, of live E.coli, of zymosan or by the CLP technique. A single dose of 50 to 250 mg/kg of the modified immunoglobulin preparation, but not of the native, commercially available IVIg significantly increased survival in all sepsis models.
The mechanisms of the protective activity of modified IVIg were studied in LPS sepsis. Its therapeutic effect was not due to a more efficient LPS neutralization and was still present when administered 6 hours after LPS. In the treated animals the serum levels of pro-inflammatory cytokines were decreased, IL10 levels were increased, the coagulation abnormality was overcome and the complement exhaustion was prevented. The exposure to Fe(II) ions induced structural changes in the IgG molecules as demonstrated by fluorescent spectroscopy, kinetic and thermodynamic analyses. These changes did not result in their denaturation as the modified preparations still met the strict Pharmacopoeia requirements for IVIg. We suggest that modified IVIg with additionally enhanced polyspecificity, induced by a brief exposure to pro-oxidative ferrous ions, has a clinical potential in sepsis and other variants of the SIRS syndrome (post-traumatic, in avian flu, etc.).
Acknowledgements
This work was supported by the Bulgarian and Swiss National Science Funds, the Pasteur Institute (Paris) and the NATO Science for Peace Program.
Keywords:
passive immunotherapy,
Systemic Inflammatory Response Syndrome,
Sepsis,
IVIgG,
Experimental models
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Vassilev
TL
(2013). Passive immunotherapy with
modified intravenous immunoglobulins (IVIg) improves survival in
experimental sepsis by attenuating inflammatory and coagulation pathways.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00698
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Tchavdar L Vassilev, Bulgarian Academy of Sciences, Sofia, Bulgaria, vassilev@microbio.bas.bg