Intravenously administered immunoglobulins (IgG) treatment has several modes of action that can regulate the immune response during different steps of the inflammatory process in experimental autoimmune encephalomyelitis (EAE) and Multiple Sclerosis (MS). The immunomodulatory effects IgG are largely dependent on their ability to interact with membrane molecules of lymphocytes and monocytes. Better understanding of these mechanisms of action in relation to the pathogenesis of MS, is important in order to decide the time of initiation and the duration of treatment in MS patients. In order to have the best beneficial effect on disease course, future research should focus on the initial events that activate the disease and on the early treatment modalities of IgG in MS.
MokhatarianVF, McFarlinDE, RaineCS. (1984) Adoptive transfer of myelin basic protein-synthesized T-cells produce chronic relapsing demyelinating disease in mice. Nature309: 356–358.
8.
AchironA (1994) Intravenous immunoglobulin treatment of experimental T-cell mediated autoimmune diseases: Up-regulation of T-cell proliferation and down-regulation of TNF-a secretion. J Clin Invest93: 600–605.
9.
AbeY, HoriuchiA, MiyakeM, KimuraS. (1994) Anticytokine nature of natural human immunoglobulin: one possible mechanism of the clinical effect of intravenous immunoglobulin therapy. Immunol Rev139: 5–19.
10.
AnderssonU, BjorkL, Skansen-SaphirU, AnderssonJ. (1994) Pooled human IgG modulates cytokine production in lymphocytes and monocytes. Immunol Rev139: 21–42.
11.
SelmajKW, RaineCS, CannellaB, BrosnanCF. (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest87: 949–954.
12.
RennoT (1994) Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice. J Neuroimmunol49: 1–7.
13.
ShariefM, ThompsonE. (1992) In vivo relationhsip of tumor necrosis factor-a to blood-brain barrier damage in patients with active multiple sclerosis. J Neuroimmunol38: 27–33.
14.
Acha-OrbeaH (1988) Limited heterogeneity of T-cell receptors from T lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell54: 263–273.
15.
MouthonL (1996) Mechanisms of action of intravenous immune globulin in immune-mediated diseases. Clin Exp Immunol104 (Suppl. 1): 3–9.
16.
MethaRL, LenertP, ZanettiM (1994) Synthetic peptides of human CD4 enhance binding of immunoglobulins to monocyte/macrophage cells. II. Mechanisms of enhancement. Cell Immunol156: 146–154.
17.
KlaessonS (1993) Immune modulatory effects of immunoglobulins on cell-mediated immune responses in vitro. Scand J Immunol38: 477–484.
18.
SbranaS (1993) In vitro effects of an immunoglobulin preparation for intravenous use (IVIG) on T-cells activation. Allerg Immunol25: 35–37.
19.
SibrowskiW, BrauerP. (1992) Effect of various plasma preparations and i.v. immunoglobulins on the function of lymphocytes and monocytes in vitro. Infusionsther Transfusionsmed19: 232–236.
20.
VizierC (1999) Role of autoreactive CD8+ T-cells in organ-specific autoimmune disease: insight from transgenic mouse. Immunol Rev169: 81–92.
21.
LeeHK, KimDS, NohGW, LeeKY. (1996) Effects of intravenous immune globulin on the peripheral lymphocyte phenotypes in Kawasaki disease. Yonsei Medical Journal37: 357–363.
22.
AukrustP (1997) Modulation of lymphocyte and monocyte activity after intravenous immunoglobulin administration in vivo. Clinical and Experimental Immunology107: 50–56.
23.
LiningtonC (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin oligodendrocyte glycoprotein. Am J Pathol130: 443–454.
24.
StorchMK (1998) Multiple sclerosis: In situ evidence for antibody- and complement-mediated demyelination. Ann Neurol43: 465–471.
25.
BastaM, DalakasM. (1994) High dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments. J Clin Invest94: 1729–1735.
26.
RodriguezM, LennonVA. (1990) Immunoglobulins promote remyelination in the central nervous system. Ann Neurol27: 12–17.
27.
RodriguezM. (1991) Immunoglobulins stimulate central nervous system remyelination: electron microscopic and morphometric analysis of proliferating cells. Lab Invest64: 358–370.
28.
StangelM, CompstonA, ScoldingNJ. (1999) Polyclonal immunoglobulins for intravenous use do not influence the behaviour of cultured oligodendrocytes. J Neuroimmunol96: 228–233.
