SummaryOur study investigated the immunomodulatory activities of human plasmaderived serum immunoglobulin (Ig)A. Previous findings seem contradictory indicating either pro-or anti-inflammatory activities. We used serum IgA purified from large plasma pools and studied the modulation of the release of cytokines and chemokines from resting and lipopolysaccharide ( We conclude that human serum IgA has both an anti-inflammatory and a pro-inflammatory capacity and this dual capacity might contribute to the feedback mechanisms maintaining a balance between pro-inflammatory and anti-inflammatory activities.

BackgroundHuman intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural anti-amyloid beta antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial effects to patients of Alzheimer’s disease (AD). Here, we set out to explore the effects of hIVIG in a mouse model of AD.MethodsWe treated APP/PS1dE9 transgenic and wild-type mice with weekly injections of a high hIVIG dose (1 g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR, and confocal microscopy.ResultsWe found no evidence for reduction in Aβ pathology; instead 8 months of hIVIG treatment significantly increased soluble levels of Aβ40 and Aβ42. In addition, we noticed a significant reduction in CD45 and elevation of Iba-1 markers in specific sub-populations of microglial cells. Long-term hIVIG treatment also resulted in significant suppression of TNF-α and increase in doublecortin positive adult-born neurons in the dentate gyrus.ConclusionsOur data indicate limited ability of hIVIG to impact amyloid burden but shows changes in microglia, pro-inflammatory gene expression, and neurogenic effects. Immunomodulation by hIVIG may account for its beneficial effect in AD patients.

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