title: 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-1beta expression. Glomerular nitrite production by isolated cultured glomeruli was reduced after IL-10 treatment in vivo (high dose: 2.3 +/- 2.3 nmol/10(4) glomeruli per 72 h; low dose: 28 +/- 5 nmol/10(4) glomeruli per 72 h; control treatment: 82 +/- 11 nmol/10(4) glomeruli per 72 h). Tumor necrosis factor-alpha 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 +/- 23 pg/10(4) 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.
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.
authors.forename: Xiou Ru
authors.initials: XR
authors.lastname: Huang
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Tipping
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D002455:Cell Division / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018932:Chemokine CCL2; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D009573:Nitrites; D019007:P-Selectin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10