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

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