title: Polyvalent immunoglobulin significantly attenuated the formation of IL-1β in Escherichia coli-induced sepsis in pigs.
abstract: Evidence suggests that adjunctive treatment with intravenous immunoglobulin preparations enriched with IgA and IgM reduce mortality in sepsis. The mode of action of polyvalent immunoglobulin is complex, including neutralization of toxins and modulation of complement activation and cytokine formation toward an anti-inflammatory profile. In this study we explored the effect of Pentaglobin, containing IgG, IgA and IgM, on the initial inflammatory reaction as well as on hemodynamics, using a well characterized and standardized porcine model of sepsis. Anesthetized and mechanically ventilated pigs, mean weight 14.9 kg, were allocated into two groups of 8 animals, receiving either Pentaglobin or saline, before sepsis was induced by intravenous Escherichia coli infusion. Five negative controls received saline only. All animals were observed for 4 h under extensive invasive monitoring. Pentaglobin significantly (p < 0.05) attenuated IL-1β formation by 38% at the end of the experiment, and markedly increased (p < 0.05) the formation of IL-10 at 60 min. TNF-α, IL-6, IL-8 and expression of the cell surface marker wCD11R3 were lower in the Pentaglobin group, but the differences were not significant. The serum concentration of LPS was three times higher in the Pentaglobin group (p < 0.005), indicating binding of LPS to Pentaglobin. Complementary in vitro experiments showed a higher binding affinity for IgM and IgA to LPS than for IgG. LPS-induced formation of IL-6 was significantly (p < 0.05) attenuated by Pentaglobin in an in vitro whole blood model. In conclusion, Pentaglobin decreased the key inflammasome IL-1β molecule in an E. coli-model of pigs sepsis.
authors.affiliation: Department of Immunology, Oslo University Hospital Rikshospitalet, University of Oslo, N-0027 Oslo, Norway. andreas.barrattdue@gmail.com
authors.forename: Andreas
authors.initials: A
authors.lastname: Barratt-Due
authors.forename: Andrey
authors.initials: A
authors.lastname: Sokolov
authors.forename: Alice
authors.initials: A
authors.lastname: Gustavsen
authors.forename: Bernt Christian
authors.initials: BC
authors.lastname: Hellerud
authors.forename: Kjetil
authors.initials: K
authors.lastname: Egge
authors.forename: Soeren Erik
authors.initials: SE
authors.lastname: Pischke
authors.forename: Julie Katrine
authors.initials: JK
authors.lastname: Lindstad
authors.forename: Anne
authors.initials: A
authors.lastname: Pharo
authors.forename: Albert
authors.initials: A
authors.lastname: Castellheim
authors.forename: Ebbe Billmann
authors.initials: EB
authors.lastname: Thorgersen
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004926:Escherichia coli / Q000187:drug effects / Q000276:immunology; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006439:Hemodynamics / Q000187:drug effects; D007070:Immunoglobulin A / Q000097:blood / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000097:blood / Q000494:pharmacology*; D016756:Immunoglobulins, Intravenous / Q000097:blood / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000097:blood; D011485:Protein Binding; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D015415:Biomarkers; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C060166:pentaglobulin