Oligodendroglia are protected from antibody-mediated complement injury by normal immunoglobulins ("IVIg'')

High-dose intravenous immunoglobulin (IVIg) treatment has become a promisin g immune therapy that can modulate the immune system at several levels, inc luding the complement cascade. Ln relation to inflammatory demyelinating di sease, there is some clinical evidence for the suppression of disease activ ity by IVIg, while a role in promoting remyelination after experimental mye lin damage has been described. Antibody and complement deposition have been implicated in the immune attack in some cases of multiple sclerosis (MS), and to investigate the mechanisms of action of IVIg, we studied the effect of IVIg using the model of complement-mediated cell injury on oligodendrogl ia in vitro. There was no effect on direct complement lysis of the oligoden droglial cell line CG4, but antibody-dependent complement damage was inhibi ted in a dose-dependent manner by IVIg. These results were confirmed with p rimary cultures of oligodendrocyte precursor cells (OPC) and oligodendrocyt es. The addition of excess C1, C3, and C4 did not influence the inhibitory effect of IVIg, implying that binding of these complement components does n ot play a role, in contrast to other experimental models of complement dama ge. F(ab')(2) immunoglobulin fragments were at least partially responsible for the effect. We conclude that IVIg may be protective in antibody-mediate d complement injury of oligodendrocytes and their progenitors, and that thi s effect is likely to be mediated via antibody binding, rather than interfe rence with complement activation. Inhibition of inflammatory mechanisms, as opposed to a direct effect on remyelinating cells, may underlie the role o f IVIg in promoting myelin repair in experimental models. (C) 2000 Elsevier Science B.V. All rights reserved.