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Anti-inflammatory Activity of IVIG Mediated Through the Inhibitory Fc Receptor
Astrid Samuelsson,Terri L. Towers,Jeffrey V. Ravetch*
The molecular basis for the anti-inflammatory property
of intravenous gamma globulin (IVIG) was investigated in a murine modelof immune thrombocytopenia. Administration of clinically protectivedoses of intact antibody or monomeric Fc fragments to wild-typeor
Fc receptor-humanized mice prevented platelet consumptiontriggered
by a pathogenic autoantibody. The inhibitory Fc receptor,FcRIIB,
was required for protection, because disruption eitherby genetic
deletion or with a blocking monoclonal antibody reversedthe
therapeutic effect of IVIG. Protection was associated withthe ability
of IVIG administration to induce surface expressionof FcRIIB on
splenic macrophages. Modulation of inhibitory signalingis thus a
potent therapeutic strategy for attenuating autoantibody-triggeredinflammatory diseases.
Laboratory of Molecular Genetics and Immunology, The Rockefeller
University, 1230 York Avenue, New York, NY 10021, USA.
*
To whom correspondence should be addressed. E-mail:
ravetch{at}rockefeller.edu
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Shih-Yao Lin and Jean-Pierre Kinet (19 January 2001) Science291 (5503), 445.
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