Advances in the understanding of the mechanism of action of IVIg.
The IgG molecule is the main component of IVIg. Commercial preparations of IVIg are derived from a pool of donors and subsequently, IVIg products contain smaller amounts of IgA and IgM antibodies as well as Th2 cytokines and cytokine antagonists that may also contribute to therapeutic effects. Numerous targets for IVIg include: T-cells, cytokines, immune cell trafficking, B-cells, complement and Fc-receptors. IVIg has been demonstrated to inactivate auto-reactive T-cells by competing for and interrupting their interaction with antigen presenting cells. The balance of cytokines also appears to be restored by IVIg, with studies showing that IVIg contains antibodies and antagonists to pro-inflammatory cytokines. In addition, IVIg is thought to interfere with and prevent the passage of auto-immune T-cells into the blood-nerve barrier. The effects of exogenous antibodies on B-cells have been well studied; IVIg is thought to down-regulate antibody production by B-cells, interfere with B-cell proliferation via a blockade of cell surface receptors and prevent the activation of certain subtypes of B-cell. In addition, IVIg can affect innate immunity by interrupting the steps in the complement activation cascade and blocking Fc-receptor mediated activity, which results in down-regulation of macrophage activity. In conclusion, IVIg has numerous modes of action, which culminate in the down-regulation of the immune response; many of which may be relevant to neuromuscular disorders and immune neuropathies.
Hartung
Hans-Peter
HP
Department of Neurology, Heinrich-Heine-University, Moorenstr. 5, 40225, Duesseldorf, Germany. hans-peter.hartung@uni-duesseldorf.de
D020274:Autoimmune Diseases of the Nervous System / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000494:pharmacology*; D009468:Neuromuscular Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D016756:Immunoglobulins, Intravenous