Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor

The molecular basis for the anti-inflammatory property of intravenous gamma globulin (IVIG) was investigated in a murine model of immune thrombocytopenia. Administration of clinically protective doses of intact antibody or monomeric Fe fragments to wild-type or Fc gamma receptor-humanized mice prevented platelet consumption triggered by a pathogenic autoantibody. The inhibitory Pc receptor, Fc gamma RIIB, was required for protection, because disruption either by genetic deletion or with a blocking monoclonal antibody reversed the therapeutic effect of IVIG. Protection was associated with the ability of IVIG administration to induce surface expression of Fc gamma RIIB on splenic macrophages. Modulation of inhibitory signaling is thus a potent therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases.