REVERSAL OF PROINFLAMMATORY RESPONSE BY LIGATING THE MACROPHAGE FC.GAMMA.RI RECEPTOR

摘要

Ligation of the Fc.gamma. receptor type I (Fc.gamma.RI) on IL-10-producingcells leads to a selective upregulation of IL-10 production, which inturn induces a marked suppression of IL-12 biosynthesis by IL-12-producingcells, particularly macrophages. The ligation of the Fc.gamma.RIreceptor thus downmodulates IL-12 production via a mechanism that is dependenton macrophage-derived IL-10. Agents for ligating Fc.gamma.RIcomprise, for example, multivalent antibodies which bind the Fc.gamma.RIreceptor, immune complexes comprising antibodies which contain theFc region of IgG, and IgG multimers, preferably IgG dimers and trimers. Theligating agent may be administered to therapeutically inhibitproinflammatory immune responses. In particular, the ligating agent may beadministered to treat or prevent endotoxic shock associatedwith bacterial endotoxemia, and to treating autoimmune disorders.