与肿瘤坏死因子-α拮抗剂或环孢素相比，降低白细胞介素-12活性可改善银屑病患者的心肌和血管功能。
Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.
作者信息
Ikonomidis Ignatios, Papadavid Evangelia, Makavos George, Andreadou Ioanna, Varoudi Maria, Gravanis Kostas, Theodoropoulos Kostas, Pavlidis George, Triantafyllidi Helen, Moutsatsou Paraskevi, Panagiotou Christina, Parissis John, Iliodromitis Efstathios, Lekakis John, Rigopoulos Dimitrios
机构信息
From the Second Department of Cardiology (I.I., G.M., M.V., G.P., H.T., J.P., E.I., J.L.), Second Department of Dermatology and Venereology (E.P., K.T., D.R.), Department of Biological Chemistry (P.M., C.P.), and Department of Clinical Biochemistry (P.M., C.P.), Attikon Hospital, National and Kapodistrian University of Athens Medical School, Greece; and Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens School of Pharmacy, Greece (I.A., K.G.).
出版信息
Circ Cardiovasc Imaging. 2017 Sep;10(9). doi: 10.1161/CIRCIMAGING.117.006283.
BACKGROUND
Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis.
METHODS AND RESULTS
One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment (<0.05). Compared with anti-TNF-α and cyclosporine, anti-IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (-25% versus -4% versus -2%), malondialdehyde (-27% versus +5% versus +26%), and NT-proBNP(-26% versus -13.6% versus 9.1%) and increase of fetuin-a (<0.01). Pulse wave velocity and augmentation index were improved only after anti-IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting-untwisting (<0.05).
CONCLUSIONS
In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857.
背景
白细胞介素（IL）-12活性参与银屑病和急性冠状动脉综合征的发病机制。我们研究了IL-12抑制对银屑病患者血管和左心室（LV）功能的影响。
方法和结果
150例银屑病患者被随机分为接受抗IL-12/23（优特克单抗，n = 50）、抗肿瘤坏死因子-α（TNF-α；依那西普，n = 50）或环孢素治疗（n = 50）。在基线和治疗后4个月，我们测量了：（1）使用斑点追踪超声心动图测量左心室整体纵向应变、扭转以及二尖瓣开放时峰值扭转与解旋之间的百分比差异（%untwMVO）；（2）冠状动脉血流储备；（3）脉搏波速度和增强指数；（4）循环中的N末端B型利钠肽原（NT-proBNP）、TNF-α、IL-6、IL-12、IL-17、丙二醛和胎球蛋白-a。与基线相比，所有患者治疗后整体纵向应变（中位数：-17.7%对-19.5%）、左心室扭转（12.4°对14°）、%untwMVO（27.8%对35%）和冠状动脉血流储备（2.8对3.1）均有所改善，循环中的NT-proBNP、IL-17、TNF-α和IL-6降低（<0.05）。与抗TNF-α和环孢素相比，抗IL-12/23治疗使整体纵向应变（25%对17%对6%）、左心室扭转（27%对17%对1%）、%untwMVO（31%对27%对17%）和冠状动脉血流储备（14%对11%对4%）有更大改善，同时IL-12（-25%对-4%对-2%）、丙二醛（-27%对+5%对+26%）和NT-proBNP（-26%对-13.6%对9.1%）降低幅度更大，胎球蛋白-a升高幅度更大（<0.01）。仅抗IL-12/23治疗后脉搏波速度和增强指数得到改善，且与整体纵向应变、左心室扭转-解旋的变化相关（<0.05）。
结论
在银屑病中，抑制IL-12/23比抑制TNF-α或环孢素治疗能更大程度地改善冠状动脉、动脉和心肌功能。
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