Reversal of proinflammatory response by ligating the macrophage FcgammaRI receptor

摘要

Ligation of the Fc receptor type I (FcRI) 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 FcRI receptor thus downmodulates IL-12 production via a mechanism that is dependent on macrophage-derived IL-10. Agents for ligating FcRI comprise, for example, multivalent antibodies which bind the FcRI 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.