Modulation of complement-mediated immune damage by intravenous immune globulin.
High-dose intravenous immune globulin (IVIG) exerts a beneficial effect in a variety of immune disorders. One possible underlying mechanism of this effect could be interference with the complement system. This conclusion was based on the results obtained in animal models of complement-mediated pathology, in vitro complement assays and studies on related human diseases. Clearance of IgM-sensitized erythrocytes was specifically suppressed by IVIG treatment. The same therapy prevented pulmonary endothelial cell lesions, the hallmark of Forssman shock, in 75% of animals. All control animals, either untreated or injected with control reagents, died within minutes following induction of Forssman shock. In vitro uptake of C3b and C4b complement fragments onto corpusculate immune complexes was significantly inhibited by IVIG. Studies that involved patients suffering from disorders with pathogenesis similar to animal models of complement-mediated immune injury fully supported the hypothesis that IVIG interacts with activated complement components and prevents their deposition on target cells. The author's results suggest that IVIG can be an effective modulator of inappropriate complement attack.
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Laboratory of Clinical Investigations, National Institute of Allergy and infectious Diseases, Bethesda, Maryland 20892, USA.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology / Q000628:therapy; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000628:therapy*; D003165:Complement System Proteins / Q000009:adverse effects*; D003882:Dermatomyositis / Q000276:immunology / Q000628:therapy; D004912:Erythrocytes / Q000276:immunology; D005577:Forssman Antigen; D006168:Guinea Pigs; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology / Q000628:therapy; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D016756:Immunoglobulins, Intravenous; D003165:Complement System Proteins; D005577:Forssman Antigen