Cell death modulation by intravenous immunoglobulin.
The induction of cell death in immune cells by naturally occurring antibodies specific for death receptors may present an important antiinflammatory mechanism of intravenous immunoglobulin (IVIG). Conversely, the protection of tissue cells from death receptor-mediated apoptosis by blocking antibodies is thought to contribute to the beneficial effects of IVIG in certain inflammatory disorders such as toxic epidermal necrolysis, also known as Lyell's syndrome. In this review, we focus on recent insights into the role of functional antibodies against Fas, sialic acid-binding immunoglobulin-like lectin (Siglec)-8, and Siglec-9 receptors in IVIG-mediated cell survival or death effects. In addition, we examine a variety of factors in inflammatory disease that may interplay with these cellular events and influence the therapeutic efficacy or potency of IVIG. These involve activation status of the target cell, cytokine microenvironment, pathogenesis and stage of disease, individual genetic determinants, species characteristics, and batch-to-batch variations of IVIG preparations.
von Gunten
Stephan
S
Institute of Pharmacology, University of Bern, Friedbühlstrasse 49, Bern, Switzerland.
Simon
Hans-Uwe
HU
D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D007518:Isoantibodies / Q000276:immunology; D037102:Lectins / Q000276:immunology; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D019014:fas Receptor / Q000276:immunology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001323:Autoantibodies; D001324:Autoantigens; C491901:FAS protein, human; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D037102:Lectins; C403967:SIGLEC8 protein, human; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D019014:fas Receptor