Normal polyclonal immunoglobulins ('IVIg') inhibit microglial phagocytosisin vitro

Phagocytosis removes pathogens and tissue debris during inflammatory reacti ons, but also plays an important role in autoimmune reactions. The main pha gocytes in the central nervous system (CNS) are microglial cells that are a ctivated during CNS inflammation. In the treatment of inflammatory demyelin ating diseases like multiple sclerosis (MS), administration of intravenous immunoglobulins (IVIg) has become a promising immunomodulatory therapy. Alt hough a large number of potential mechanisms for the effects of IVIg has be en suggested, the precise mode of action in CNS inflammation is unknown. We assessed the influence of IVIg on phagocytosis and endocytosis in microgli a in vitro. IVIg had little effect on non-specific phagocytosis of latex pa rticles in untreated microglia, while there was a dose-dependent inhibition in microglia activated with LPS and IFN gamma. Endocytosis of soluble myel in basic protein (MBP) was downregulated by IVIg in both untreated and acti vated microglia. The effect was mediated by an F(ab')(2) preparation of imm unoglobulins, suggesting that Fc receptor-mediated phagocytosis is not invo lved. Intact IVIg, bur not F(ab')(2) fragments also suppressed Fc receptor- mediated phagocytosis of opsonised erythrocytes in both untreated and activ ated microglia. These results show that IVIg can inhibit the phagocytic act ivity of microglia via different mechanisms. Such an effect could contribut e to the immunomodulatory capacity of IVIg in inflammatory CNS diseases. (C ) 2000 Elsevier Science B.V. All rights reserved.