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 thrombocytope nia. Administration of clinically protective doses of intact antibody or mo nomeric Fe fragments to wild-type or Fc gamma receptor-humanized mice preve nted platelet consumption triggered by a pathogenic autoantibody. The inhib itory Pc receptor, Fc gamma RIIB, was required for protection, because disr uption either by genetic deletion or with a blocking monoclonal antibody re versed the therapeutic effect of IVIG. Protection was associated with the a bility of IVIG administration to induce surface expression of Fc gamma RIIB on splenic macrophages. Modulation of inhibitory signaling is thus a poten t therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases.