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.