Gaining More From Gamma Globulins

he use of intravenous immunoglobulin (IVIg), which is immunoglobulin G pooled from thousands of healthy donors, in the treatment of immunodeficient and autoimmune diseases has grown during the past 2 decades. Although its initial application was largely limited to replacement therapy in hypogammaglobulinemia, IVIg is gaining acceptance as therapy for autoimmune thrombocyto- penia purpura, and a number of other autoimmune diseases such as multiple sclerosis.1 Although the exact mechanisms underlying the protection conferred by IVIg in these immune disorders remain undefined, several potential molecular and cellular targets have been proposed. For example, IVIg can block Fc receptors on macrophages and effector cells to reduce the phagocytic capacity of these cells. IVIg may also regulate the immune response by reacting with a number of membrane receptors on T cells, B cells, and monocytes that are pertinent to autoreactivity and induction of tolerance to self.1 Recent work has also revealed a beneficial effect of IVIg in systemic inflammatory disorders such as sepsis and asthma. It has been suggested that IVIg may exert its antiinflammatory effects by attenuating complement- mediated attack,2 inducing antiinflammatory cytokines, and reducing the production of proinflammatory cytokines such as tumor necrosis factor-, interferon- and interleukin-13 (Figure). Many of these mechanistic studies of IVIg effects on the inflammatory response are based on in vitro models and in vivo data are lacking.