Interleukin-1 receptor antagonist modulates the progression of a spontaneously occurring IgA nephropathy in mice

Ann Chen, Lai Fa Sheu, Wei Yuan Chou, Shin Chang Tsai, Deh Ming Chang, San Chi Liang, Fu Gong Lin, Wei Hwa Lee

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Cytokines, such as interleukin-I (IL-1), may play a key role in the pathogenesis of IgA nephropathy (IgAN). This study was conducted to evaluate the effects of IL-1 receptor antagonist (IL-1ra) in the treatment of a spontaneously occurring experimental IgAN in established phase. ddY mice (12/group) were injected twice daily with 3 mg/kg of IL-1ra, intraperitoneally, for 8 consecutive weeks. The placebo mice were injected with saline only. As normal controls, ddY mice, which were not treated with IL-1ra or saline, were killed at 6 weeks of age. Results showed a significant reduction of proteinuria in the IL-1ra-treated mice, compared with saline- treated mice (urinary albumin/creatinine, 0.24 ± 0.04 v 0.39 ± 0.03, P < 0.001). A significant improvement of renal 51Cr-EDTA (ethylenediaminetetra- acetic acid) clearance was observed in the IL-1ra-treated mice (t 1/4 , 12 ± 2.7 minutes, compared with saline-treated mice 25 ± 2.0 minutes, P < 0.001). Similarly, serum levels of creatinine (1.0 ± 0.4 v 2.4 ± 0.3 mg/dL, P < 0.001) and urea nitrogen (46 ± 6 v 58 ± 2 mg/dL, P < 0.01) were significantly lower in IL-1ra-treated mice than in saline-treated mice. In renal tissue studies, the IL-1ra-treated mice exhibited significantly decreased mesangial cell proliferation, compared with saline-treated mice (P < 0.001), as shown by light and electron microscopy. In addition, the IL- 1ra-treated mice showed significantly lower glomerular expression of collagen type IV, fibronectin, laminin, and IL-6 (P < 0.001) than saline-treated mice, although they still showed higher glomerular expression of collagen type IV (P < 0.01), fibronectin (P < 0.01), laminin (P <: 0.001), IL-1 (P < 0.001), and IL-6 (P < 0.01) than did normal control mice. Meanwhile, glomerular C3 deposition was significantly lower in IL-1ra-treated mice than in saline- treated mice (P < 0.001). These findings indicate that IL-1ra partially prevented the progression of spontaneously occurring IgAN in this experimental model. Data from these experiments also confirm the pathogenic effects of IL-1 in the established phase of IgAN in ddY mice.

Original languageEnglish
Pages (from-to)693-702
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume30
Issue number5
DOIs
Publication statusPublished - Nov 1997
Externally publishedYes

Keywords

  • IgA nephropathy
  • Interleukin- 6
  • Interleukin-1 receptor antagonist
  • Mesangial cell
  • ddY mice

ASJC Scopus subject areas

  • Nephrology

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