Administration of IgG Fc fragments prevents glomerular injury in experimental immune complex nephritis

Most human nephritis is due to glomerular deposition and/or formation of im mune complexes (IC), In cultured mesangial cells, Fc receptor stimulation i nduces proliferation, matrix synthesis, and release of several mediators im plicated in the initiation and progression of glomerular injury. Since Ig F c fragments in vitro modified these phenomena, we studied the effect of sys temic administration of IgG Fc fragments on the evolution of experimental I C nephritis, Fc fragment injection (1 mg/day i.p.) to rats with ongoing nep hritis (proteinuria 20-50 mg/24 h vs 9 +/- 0.2 mg/24 h in controls) markedl y ameliorates proteinuria, renal function, and morphological renal lesions. This was accompanied by a reduction in the renal synthesis of chemokines ( monocyte chemoattractant protein-1, IFN-inducible protein-10, and cytokine- induced neutrophil chemoattractant-1), matrix proteins, and growth factors (platelet-derived growth factor, and TGF-beta), and in the activity of tran scription factors, The treatment did not affect the glomerular deposition o f IgG IC and complement C1q, In contrast, a decrease in the renal expressio n and production of C3 was observed without changes in serum complement lev els. In vitro, very low complement consumption and no C3b covalent interact ion were observed,vith Fc fragments, confirming that they did not modify sy stemic complement activity. These results indicate that the administration of Fc fragments prevents the development of glomerular damage in an aggress ive model of proliferative glomerulonephritis through mechanisms involving a reduced local generation of complement, chemokines and growth factors. Mo dulation of IC-mesangial cell interaction by Fc fragment administration cou ld represent a new approach to the treatment of severe immune nephritis, Th e Journal of Immunology, 2000, 164: 2092-2101.