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.

Interleukin 6 (IL-6) Deficiency Delays Lupus Nephritis in MRL-FaslprMice: The IL-6 Pathway as a New Therapeutic Target in Treatment of Autoimmune Kidney Disease in Systemic Lupus Erythematosus

“…Data from a study with rats that overexpressed IL-10 31 correlate with our findings that renal interstitial infiltration and renal expression of monocytes/macrophages, CD8+, and CD4+ T cells were reduced. Further studies showed that IL-10 is capable of inhibiting mesangial proliferative glomerulonephritis through inhibition of macrophage-induced glomerular injury 32,33 . MRL-Fas lpr mice with IL-10 deficiency developed exacerbated disease with heavy glomerulonephritis 34 .…”

Identification and Validation of Prognostic Biomarkers Specifically Expressed in Macrophage in IgA Nephropathy Patients Based on Integrated Bioinformatics Analyses

“…The protein encoded by IL10RA is a receptor for interleukin 10 (IL-10). IL-10 is a multifunctional immune regulator in diverse inflammatory diseases, including kidney disease ( Huang et al, 2000 ; Diefenhardt et al, 2018 ). The effect of IL10RA upregulation on macrophages in glomerulopathy has not been well illustrated.…”

IL-10/β-Endorphin-Mediated Neuroimmune Modulation on Microglia during Antinociception

“…Liou and colleagues [51] evaluated Met-RANTES intraperitoneal administration in mice with neuropathic pain, and found that this treatment reduced mechanical allodynia after sciatic nerve ligation, increasing IL-10 and reducing macrophage infiltration and β-endorphin expression [51]. Increased IL-10 levels accompanied by reduced macrophage infiltration would explain the impossibility of IL-10-induced β-endorphin expression, since the same group previously showed that opioid peptides are initially secreted by neutrophils and later by macrophages [51,53,54].…”