IMMUNOMODULATION AND REMYELINATION - 2 ASPECTS OF HUMAN POLYCLONAL IMMUNOGLOBULIN TREATMENT IN IMMUNE-MEDIATED NEUROPATHIES

Intravenous immunoglobulin is used in inflammatory demyelinating disea ses 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 differe nt models of T and B cell activation were investigated. IVIg inhibited a predominantly cellular immune response of the Th I type which was p artially reversed by addition of Th I cytokines. In contrast in a mode l,;which leeds to B cell differentiation and antibody production, a sy nergistic stimulatory effect of IVIg and Th2 cytokines was observed. T he ability of IVIg to interfere with cell proliferation and to manipul ate the Th1/Th2 profile will have consequences for the induction, char acter, and amplification of on immune response. Apart from the immunom odulatory effects evidence shows that IVIg promote remyelination not o nly by abrogation of the auto-immune attack but also by on effect an g lial cells. We showed that IVIg induce growth arrest of normal human f ibroblasts and Shwann cells. In fibroblasts this growth arrest is acco mpanied by upregulation of GA5-3/PMP-22 mRNA. The implications of this finding ore discussed. Further studies in human Schwann cells ore imp erative to prove the hypothesis that IVIg directly stimulates remyelin ation.