Blocking of interleukin-1 suppresses angiotensin II-induced renal injury

Koji Akita, Kikuo Isoda, Fumie Ohtomo, Sarasa Isobe, Tomiharu Niida, Yayoi Sato-Okabayashi, Motoaki Sano, Kazunori Shimada, Yoichiro Iwakura, Tohru Minamino

研究成果: Article査読

抄録

Clinical hypertension (HT) is associated with renal inflammation and elevated circulating levels of proinflammatory cytokines. Interleukin (IL)-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines and plays a crucial role in inflammation. Inhibition of IL-1 may contribute to modulation of the Angiotensin II (Ang II)-induced HT response. The present study aimed to elucidate the effects of IL-1Ra and anti-IL-1β antibody (01BSUR) on Ang II-induced renal injury. To determine the contribution of IL-1Ra to Ang II-induced renal inflammation, male wildtype (WT) and IL-1Ra-deficient (IL-1Ra−/−) mice were infused with Ang II (1000 ng/kg/min) using subcutaneous osmotic pump for 14 days. We checked renal function, histological change, and several mRNA expressions 14 days after infusion. Fourteen days after infusion, systolic blood pressure (197 + 5 vs 169 + 9 mmHg, P<0.05) in IL-1Ra−/− mice significantly increased compared with WT mice. Furthermore, on day 14 of Ang II infusion, plasma IL-6 was 5.9-fold higher in IL-1Ra−/− versus WT mice (P<0.001); renal preproendothelin-1 mRNA expression was also significantly higher in IL-1Ra−/− mice (P<0.05). In addition, renal histology revealed greater damage in IL-1Ra−/− mice compared with WT mice 14 days after infusion. Finally, we administrated 01BSUR to both IL-1Ra−/− and WT mice, and 01BSUR treatment decreased Ang II-induced HT and renal damage (glomerular injury and fibrosis of the tubulointerstitial area) in both IL-1Ra−/− and WT mice compared with IgG2a treatment. Inhibition of IL-1 decreased Ang II-induced HT and renal damage in both IL-1Ra−/− and WT mice, suggesting suppression of IL-1 may provide an additional strategy to protect against renal damage in hypertensive patients.

本文言語English
ページ(範囲)2035-2048
ページ数14
ジャーナルClinical Science
135
17
DOI
出版ステータスPublished - 2021 9

ASJC Scopus subject areas

  • 医学(全般)

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