Evaluation and review: Symposium covers indications for the use of intravenous immunoglobulin☆☆☆

Immunoglobulins are a heterogeneous group of humoral antibodies produced in response to antigen stimulation. For the most part, therapeutic immunoglobulins represent polyvalent immunoglobulins derived from thousands of donors, hyperimmune immunoglobulins directed toward single antigens or infectious agents, or the more recent engineered immunoglobulins with monoclonal specificity that are used for targeted immunotherapy. The intent of the meeting was to evaluate and review the current indications for the use of intravenous immunoglobulin (IVIG). Discussions included IVIG’s pathogenesis and mechanisms of action in various disease states, safety issues, and problems related to availability. One goal of the meeting was to develop a current consensus on IVIG use and safety. Although many articles have been written about immunomodulant high-dose, IVIG therapy, its action mechanisms are more complex than simple “reticuloendothelial blockade.” Speakers at this symposium considered state-of-the-art immunoglobulin therapy but also focused on action mechanisms and, in particular, an appreciation of the role of inflammatory cytokines, adhesion molecules, and cellular receptors in replacement and immunomodulatory therapy. Advances in IVIG purification and specificity refinement have been achieved recently by implementing purification strategies, in particular solvent and detergent treatment. The safety issues were addressed in terms of reducing side effects, processing advancements, and pathogen safety in both IVIG and other human plasmaderived therapeutic proteins. A presentation by Miller et al addressed this issue. They emphasized that even though pathogen safety records for IVIG and other plasma proteins are excellent, the industry remains active in improving the safety margin. Their paper focused on strategies designed to eliminate the potential for transmitting known and unknown infectious agents. Considering action mechanisms and broader applications of intravenous gamma globulin therapy, Ott et al addressed the FcγRIIB receptor as a potential molecular target. Their article addressed the role of cell surface inhibitory receptors in attenuating immune responses and their role in activating any inhibitory signals. Further discussion also focused on IVIG’s immunomodulatory and anti-inflammatory effects with a shift in focus towards organ-specific applications in special circumstances. Issues addressed included the regulation of innate immunity, IVIG’s role in apoptosis, and Fc receptor function and its influence on cytokine cascades. Modlin presented the role of toll-like receptors in human innate immune responses to microbial pathogens. Toll-like receptors seem to integrate after their activation with other aspects of host defense mechanisms such as the activation of cytokines, including IL-12 and other host defense mechanisms. His article addressed the intricate dynamics of the cytokine receptor cascade’s enhancement of innate immunity. The role of humoral immune responses in microbial defense mechanisms is well appreciated. New applications in other infectious diseases also have been addressed. To this end, the potential use of intravenous Evaluation and review: Symposium covers indications for the use of intravenous immunoglobulin