Shen C, Assche G V, Colpaert S, Maerten P, Geboes K, Rutgeerts P, Ceuppens J L
Laboratory of Experimental Immunology, Catholic University, Leuven, Belgium.
Aliment Pharmacol Ther. 2005 Feb 1;21(3):251-8. doi: 10.1111/j.1365-2036.2005.02309.x.
Adalimumab, a fully human monoclonal antibody to tumour necrosis factor, was recently introduced for therapy of Crohn's disease.
Since induction of apoptosis of inflammatory cells is thought to be an important mechanism of action of the antitumour necrosis factor monoclonal antibody infliximab, we studied the induction of apoptosis of activated peripheral blood monocytes by adalimumab.
Apoptosis was analysed at the levels of the cell membrane, mitochondria and DNA by flow cytometry.
We found that both adalimumab and infliximab induced apoptosis in cultured monocytes, while etanercept did not. Apoptosis induction was caspase-dependent and detectable already after 2 h. The production of interleukin-10 and interleukin-12 by monocytes was down-regulated significantly by adalimumab and infliximab but not by etanercept, while levels of soluble tumour necrosis factor in monocyte cultures were down-regulated by all three reagents.
These data show that both adalimumab and infliximab affect monocyte cytokine production and induce apoptosis of activated monocytes. Our findings will have to be further correlated to therapeutic efficacy of these antitumour necrosis factor reagents.
阿达木单抗是一种完全人源化的肿瘤坏死因子单克隆抗体,最近被用于治疗克罗恩病。
由于诱导炎症细胞凋亡被认为是抗肿瘤坏死因子单克隆抗体英夫利昔单抗的重要作用机制,我们研究了阿达木单抗对活化外周血单核细胞凋亡的诱导作用。
通过流式细胞术在细胞膜、线粒体和DNA水平分析凋亡情况。
我们发现阿达木单抗和英夫利昔单抗均可诱导培养的单核细胞凋亡,而依那西普则不能。凋亡诱导是半胱天冬酶依赖性的,在2小时后即可检测到。阿达木单抗和英夫利昔单抗可显著下调单核细胞产生白细胞介素-10和白细胞介素-12的水平,但依那西普则无此作用,而三种试剂均可下调单核细胞培养物中可溶性肿瘤坏死因子的水平。
这些数据表明,阿达木单抗和英夫利昔单抗均可影响单核细胞细胞因子的产生,并诱导活化单核细胞凋亡。我们的发现还需进一步与这些抗肿瘤坏死因子试剂的治疗效果相关联。