Interleukin-10 inhibits macrophage-induced glomerular injury

The ability of interleukin-10 (IL-10) to inhibit macrophage recruitment, ac tivation, and proliferation in vivo was studied in a macrophage-mediated, b ut T cell-independent, passive anti-glomerular basement membrane antibody-i nduced model of glomerulonephritis (GN) in rats. Treatment with recombinant murine IL-10 resulted in dose-dependent reductions in proteinuria (high do se: 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]; l ow dose: 5.5 +/- 0.2 c/gcs; control treatment: 12.1 +/- 0.6 c/gcs). Macroph age and intrinsic glomerular cell proliferation were reduced at both doses of IL-10, as was glomerular expression of P-selectin and monocyte chemoattr actant protein-1. IL-10 treatment also resulted in a dose-dependent reducti on of macrophage activation as indicated by MHC class II and IL-1 beta expr ession. Glomerular nitrite production by isolated cultured glomeruli was re duced after IL-10 treatment in vivo (high dose: 2.3 +/- 2.3 nmol/10(4) glom eruli per 72 h; low dose: 28 +/- 5 nmol/10(4) glomeruli per 72 h; control t reatment: 82 +/- 11 nmol/10(4) glomeruli per 72 h). Tumor necrosis factor-c t production was abolished by high-dose treatment and reduced by the lower dose (3.8 +/- 3.8 pg/10(4) glomeruli per 72 h; control treatment: 249 +/- 2 3 pg/10(4) glomeruli per 72 h). These studies demonstrate that IL-10 direct ly attenuates glomerular macrophage recruitment, activation, and proliferat ion in vivo and can significantly attenuate macrophage-mediated GN independ ent of any effects on T cells.