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

Ann Chen, Lai F. Sheu, Wei Yuan Chou, Shin Chang Tsai, Deh Ming Chang, San C. Liang, Fu Gong Lin, Wei H. Lee

Research output: Contribution to journalArticle

25 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

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

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Interleukin-1 Receptors
Immunoglobulin A
Collagen Type IV
Interleukin-1
Fibronectins
Creatinine
Interleukin 1 Receptor Antagonist Protein
Kidney
Mesangial Cells
Laminin
Proteinuria
Edetic Acid
Acetic Acid
Urea
Albumins
Interleukin-6
Electron Microscopy
Nitrogen

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Interleukin-1 receptor antagonist modulates the progression of a spontaneously occurring IgA nephropathy in mice. / Chen, Ann; Sheu, Lai F.; Chou, Wei Yuan; Tsai, Shin Chang; Chang, Deh Ming; Liang, San C.; Lin, Fu Gong; Lee, Wei H.

In: American Journal of Kidney Diseases, Vol. 30, No. 5, 11.1997, p. 693-702.

Research output: Contribution to journalArticle

Chen, A, Sheu, LF, Chou, WY, Tsai, SC, Chang, DM, Liang, SC, Lin, FG & Lee, WH 1997, 'Interleukin-1 receptor antagonist modulates the progression of a spontaneously occurring IgA nephropathy in mice', American Journal of Kidney Diseases, vol. 30, no. 5, pp. 693-702.
Chen, Ann ; Sheu, Lai F. ; Chou, Wei Yuan ; Tsai, Shin Chang ; Chang, Deh Ming ; Liang, San C. ; Lin, Fu Gong ; Lee, Wei H. / Interleukin-1 receptor antagonist modulates the progression of a spontaneously occurring IgA nephropathy in mice. In: American Journal of Kidney Diseases. 1997 ; Vol. 30, No. 5. pp. 693-702.
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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",
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AU - Tsai, Shin Chang

AU - Chang, Deh Ming

AU - Liang, San C.

AU - Lin, Fu Gong

AU - Lee, Wei H.

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AB - 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

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