title: Anti-inflammatory effect of intravenous immunoglobulin mediated through modulation of complement activation.
abstract: Complement activation by immune complexes is well-known. In the course of autoimmune disease, acute and chronic complement activation is the primary inducer of inflammation and tissue damage. Polyclonal, polyspecific intravenous immunoglobulin (IVIg) preparations are a therapy of choice in a variety of autoimmune and inflammatory diseases. This review describes mechanisms by which IgG reduces complement activation or interferes with the action of proinflammatory complement-derived proteins. The known interference of IVIg with the biological activity of complement-derived proinflammatory proteins does not affect the generation of these potentially dangerous products, but can limit their devastating effects. Therefore, we embarked on studies on IVIg's potential to attenuate complement activation and thus to prevent further generation of such dangerous molecules. We present here a revised view of how the central event of complement activation--namely, complement amplification--operates on a molecular level and how IVIg, with its physiological autoantibodies directed against some complement proteins, is able to downregulate amplification of complement C3 activation. Finally, we summarize results of a study in which clinical effects of IVIg and attenuation of complement activation were assessed. We propose that the anti-inflammatory effect of IVIg in a wide range of autoimmune diseases might be explained, at least in part, by attenuation of complement amplification.
authors.affiliation: Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich, Switzerland.
authors.forename: Hans U
authors.initials: HU
authors.lastname: Lutz
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Späth
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D018448:Models, Immunological
chemical_list: D016756:Immunoglobulins, Intravenous