Protective mechanisms of IVIG

IVIG therapeutic action likely includes several discrete mechanisms of action that kinetically may be distinct (Figure 2); blocking effects of phagocytic Fcγ receptors by IgG multimers would be immediate-acting and transient (hours), while FcRn blocking would lead to decreased autoantibody serum levels over several days. In contrast, the induction of regulatory monocytes/DCs might instead have sustained anti-inflammatory consequences on the chronic inflammatory response. In particular the inhibition of dendritic cell activation and dampening of the IFN-γ response would be expected to block both the adaptive T cell response and its pro-inflammatory consequences. The cellular and molecular details underlying the induction of the IVIG immunosuppressive program are likely to reveal new insights into our understanding of IgG immunobiology and provide new strategies for the design of more effective immunotherapeutics. © 2007 Elsevier Ltd. All rights reserved.