Validation of efficiency of anti-cytokine therapy for suppression of hypertension and organ damage

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09522
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Juntendo University
• Principal Investigator: Isoda Kikuo 順天堂大学, 医学(系)研究科(研究院), 准教授 (00532475)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アンジオテンシン / 炎症 / サイトカイン / 動脈瘤 / IL-1β中和抗体 / IL-6受容体拮抗薬

Outline of Final Research Achievements

Wild-type (WT) and IL-1Ra-deficient (IL-1Ra-/-) mice were infused with Ang II using subcutaneous osmotic pumps for 28 days. However 28-day infusion with Ang II in IL-1Ra－/－ mice significantly increased the occurrence of fatal aortic rupture (p<0.0001). Then,both types of mice were infused with Ang II for only 14 days, and histological analyses were performed at 28 days. Interestingly, abdominal aortic aneurysm (AAA) in IL-1Ra-/- mice increased more significantly than those in WT mice (89% vs. 6%,p<0.001), although SBP did not differ at 28 days in either IL-1Ra-/- and WT mice (117±4 vs 115±3 mmHg, p=0.71). Histological analyses revealed numerous inflammatory cells around the abdominal aorta in IL-1Ra-/-, but not WT mice. Finally, we determined that treatment with 01BSUR decreased Ang II-induced AAA in IL-1Ra-/- mice compared with IgG2a treatment. These results suggest suppression of IL-1 may provide an additional strategy to protect against AAA in hypertensive patients.

Free Research Field

分子血管学

Academic Significance and Societal Importance of the Research Achievements

我々は、Ang II負荷誘導の腹部大動脈瘤形成抑制にIL-1β中和抗体が有効であることを示した。さらに、動脈硬化抑制にIL-6受容体抗体が有効でることも実証した。これらの結果は動脈瘤や動脈硬化形成に抗サイトカイン療法が有効であることを示唆しており、新たな観点からの治療法開発につながると思われる。更に、抗サイトカイン療法により、動脈瘤の外科手術を減らすことが可能となれば、医療経済負担の軽減にもつながり、社会的意義が高いと考えられる。