Enhanced Anti-Diabetogenic Effect of Intravenous Immune Globulin Modified by Ferrous Ion Exposure

Abstract

The aim of this study was to investigate the immunomodulatory capacity of native and Fe(II)-exposed intravenous immune globulin (IVIg) in multiple low dose streptozotocin-induced diabetes and to delineate the mechanisms of their influence on immune cell functions. Optimal doses (200–600mg/kg) of IVIg prevented the development of hyperglycemia, glycosuria and attenuated mononuclear cell infiltration in pancreatic islets. Fe(II) exposure of IVIg decreased their optimal therapeutic dose to 100mg/kg which significantly decreased the serum levels of proinflammatory cytokines compared to the same dose of native IVIg. This was accompanied by lower numbers of TNF-α, IFN-γ and IL-17 producing CD4 + T cells and increased frequencies of CD4 + IL-10 + and CD4 + IL-4 + T cells in the pancreatic lymph nodes and islets on day 16 after diabetes induction. Ferrous ion-exposed IVIg enhanced the bias towards Th2 response while the regulatory Foxp3 + T cells were not affected.