Differential effects of anti-TNF-α and anti-IL-12/23 agents on human leukocyte-endothelial cell interactions
Differential effects of anti-TNF-α and anti-IL-12/23 agents on human leukocyte-endothelial cell interactions
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DOI：
10.1016/j.ejphar.2015.08.054
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发表时间：
2015-10-15
影响因子：
5
通讯作者：
Alvarez, Angeles
中科院分区：
文献类型：
--
作者：
Rios-Navarro, Cesar;de Pablo, Carmen;Alvarez, Angeles
增强的白细胞募集是一种炎症过程，发生在动脉粥样硬化的特征性血管功能障碍的早期阶段。我们评价了抗TNF-α（阿达木单抗、英夫利昔单抗和依那西普）和抗IL-12/23（优特克单抗）对重现体内条件的流动室中人白细胞和内皮细胞之间相互作用的影响。根据与炎症和动脉粥样硬化相关的各种内皮细胞（TNF-α、白细胞介素-1 β、α-光敏素和血管紧张素II）和白细胞（PAF、IL-12和IL-23）刺激诱导的白细胞募集，评价抗TNF-α的临床浓度。即使在建立TNF-α诱导的炎症状态之前或之后，用抗TNF-α治疗也会减少这种刺激诱导的白细胞-内皮细胞相互作用。我们的研究结果还涉及粘附分子（ICAM-1，VCAM-1和E-选择素）在抗TNF-α的白细胞粘附内皮细胞方面的作用。然而，抗TNF-α药物并不影响白细胞介素-1 β的作用，但阻止了α-光敏素和血管紧张素-II的作用。然而，一旦建立，由后三种刺激引起的炎症反应不能逆转。用抗TNF-α预处理也阻止了IL-23对PBMC滚动流量和滚动速度以及IL-12对PMN粘附诱导的白细胞作用。乌司奴单抗表现出更谨慎的特征，对任何内皮刺激诱导的白细胞募集没有影响，同时阻断IL-23对白细胞活化的影响以及IL-12对PMN粘附和PAF对PBMC滚动速度的影响。这些发现支持了生物抗炎药，特别是抗TNF-α，能够通过改善血管炎症来影响银屑病和类风湿性关节炎伴随的心血管风险的观点。(C)2015作者由爱思唯尔公司出版
Enhanced leukocyte recruitment is an inflammatory process that occurs during early phases of the vascular dysfunction that characterises atherosclerosis. We evaluated the impact of anti-TNF-alpha (adalimumab, infliximab and etanercept) and anti-IL-12/23 (ustekinumab) on interactions between human leukocytes and endothelial cells in a flow chamber that reproduced in vivo conditions. Clinical concentrations of anti-TNF-alpha were evaluated on the leukocyte recruitment induced by a variety of endothelial (TNF-alpha, interleukin-1 beta, lymphotoxin-alpha and angiotensin-II) and leukocyte (PAF, IL-12 and IL-23) stimuli related to inflammation and atherosclerosis. Treatment with anti-TNF-alpha, even before or after establishing the inflammatory situation induced by TNF-alpha, diminished leukocyte-endothelial cell interactions induced by this stimuli. Our results also implicated adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in the actions of anti-TNF-alpha in terms of leukocyte adhesion to endothelium. However, anti-TNF-alpha drugs did not influence the actions of interleuldn-1 beta, but prevented those of lymphotoxin-alpha and angiotensin-II. However, once established, inflammatory response elicited by the latter three stimuli could not be reversed. Pre-treatment with anti-TNF-alpha, also prevented leukocyte actions induced by IL-23 on PBMC rolling flux and rolling velocity and by IL-12 on PMN adhesion. Ustekinumab exhibited a more discreet profile, having no effect on leukocyte recruitment induced by any of the endothelial stimuli, while blocking the effects of IL-23 on leukocyte activation and those of IL-12 on PMN adhesion and PAF on PBMC rolling velocity. These findings endorse the idea that biological anti-inflammatory drugs, in particular anti-TNF-alpha, have the capacity to influence cardiovascular risk accompanying psoriasis and rheumatoid arthritis by ameliorating vascular inflammation. (C) 2015 The Authors. Published by Elsevier B.V.