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Intravenous immunoglobulin (IVIg) is used to treat a number of inflammatory diseases including sepsis. The objective of this study was to evaluate whether NLRP10, postulated as a negative regulator of inflammasome activation, can play a role in the anti-inflammatory effects observed in the treatment of severe sepsis with IVIg. Human peripheral blood monocytes were isolated and treated either with LPS or IVIg, or alternatively treated first with LPS followed by addition of IVIg. The induction of IL-1β and IL-18 was used as an index of inflammasome activation. Treatment of resting monocytes with IVIg resulted in a significant increase in the expression of NLRP10. LPS but not IVIg resulted in a significant increase in both IL-1β and IL-18 protein release, consistent with inflammasome activation. Furthermore, addition of IVIg to LPS-treated monocytes resulted in a significant increase in the expression of NLRP10 which was associated with a complete inhibition of both IL-1β and IL-18 increased expression. These data suggest that the IVIg-mediated induction of NLRP10 expression in monocytes contributes to the control of inflammation during sepsis and thus highlight a complementary mechanism by which IVIg exerts their anti-inflammatory effects in sepsis.

NLRP10 A Potential Contributor to the Anti-Inflammatory Effects of IVIg in Sepsis