Reversal of proinflammatory response by ligating the macrophage FcγRI receptor

Abstract

Ligation of the Fcγ receptor type I (FcγRI) on IL-10-producing cells leads to a selective upregulation of IL-10 production, which in turn induces a marked suppression of IL-12 biosynthesis by IL-12-producing cells, particularly macrophages. The ligation of the FcγRI receptor thus downmodulates IL-12 production via a mechanism that is dependent on macrophage-derived IL-10. Agents for ligating FcγRI comprise, for example, multivalent antibodies which bind the FcγRI receptor, immune complexes comprising antibodies which contain the Fc region of IgG, and IgG multimers, preferably IgG dimers and trimers. The ligating agent may be administered to therapeutically inhibit proinflammatory immune responses. In particular, the ligating agent may be administered to treat or prevent endotoxic shock associated with bacterial endotoxemia, and to treating autoimmune disorders.

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