Intravenous immunoglobulin is used in inflammatory demyelinating diseases of the peripheral as well as the central nervous system. It is not known which mechanism(s) accounts for the beneficial effect observed in these diseases. The immunomodulatory effects of IVIg in two different models of T and B cell activation were investigated. IVIg inhibited a predominantly cellular immune response of the Th 1 type, which was partially reversed by addition of Th 1 cytokines. In contrast, in a model, which leads to B cell differentiation and antibody production, a synergistic stimulatory effect of IVIg and Th2 cytokines was observed. The ability of IVIg to interfere with cell proliferation and to manipulate the Th 1/Th2 profile will have consequences for the induction, character, and amplification of an immune response. Apart from the immunomodulatory effects, evidence shows that IVIg promote remyelination not only by abrogation of the auto-immune attack but also by an effect on glial cells. We showed that IVIg induce growth arrest of normal human fibroblasts and Schwann cells. In fibroblasts this growth arrest is accompanied by upregulation of GAS-3/PMP-22 mRNA. The implications of this finding are discussed. Further studies in human Schwann cells are imperative to prove the hypothesis that IVIg directly stimulates remyelination.
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