Interleukin-10 Inhibits Macrophage-Induced Glomerular Injury

Abstract

The ability of interleukin-10 (IL-10) to inhibit macrophage recruitment, activation, and proliferation in vivo was studied in a macrophage-mediated, but T cell-independent, passive anti-glomerular basement membrane antibody-induced model of glomerulonephritis (GN) in rats. Treatment with recombinant murine IL-10 resulted in dose-dependent reductions in proteinuria (high dose: 16 ± 1 mg/24 h; low dose: 30 ± 2 mg/24 h; control treatment: 69 ± 6 mg/24 h; normal: 7 ± 1 mg/24 h) and glomerular macrophage recruitment (high dose: 1.8 ± 0.1 macrophages per glomerular cross section [c/gcs]; low dose: 5.5 ± 0.2 c/gcs; control treatment: 12.1 ± 0.6 c/gcs). Macrophage and intrinsic glomerular cell proliferation were reduced at both doses of IL-10, as was glomerular expression of P-selectin and monocyte chemoattractant protein-1. IL-10 treatment also resulted in a dose-dependent reduction of macrophage activation as indicated by MHC class II and IL-1β expression. Glomerular nitrite production by isolated cultured glomeruli was reduced after IL-10 treatment in vivo (high dose: 2.3 ± 2.3 nmol/104 glomeruli per 72 h; low dose: 28 ± 5 nmol/104 glomeruli per 72 h; control treatment: 82 ± 11 nmol/104 glomeruli per 72 h). Tumor necrosis factor-α production was abolished by high-dose treatment and reduced by the lower dose (3.8 ± 3.8 pg/104 glomeruli per 72 h; control treatment: 249 ± 23 pg/104 glomeruli per 72 h). These studies demonstrate that IL-10 directly attenuates glomerular macrophage recruitment, activation, and proliferation in vivo and can significantly attenuate macrophage-mediated GN independent of any effects on T cells.