Popa C, van Tits L J H, Barrera P, Lemmers H L M, van den Hoogen F H J, van Riel P L C M, Radstake T R D J, Netea M G, Roest M, Stalenhoef A F H
Department of Rheumatology, Radboud University Nijmegen Medical Centre, The Netherlands.
Ann Rheum Dis. 2009 Jun;68(6):868-72. doi: 10.1136/ard.2008.092171. Epub 2008 Jul 17.
High-density lipoprotein (HDL) antiatherogenic functions seem to be diminished during inflammatory conditions such as rheumatoid arthritis (RA). The aim of this study was to investigate the effects of tumour necrosis factor (TNF) inhibition on the antioxidative capacity of HDL in RA.
Plasma lipids and paraoxonase (PON-1) activity were investigated in 45 RA patients, before and during 6 months of anti-TNF therapy. In addition, HDL was isolated and tested for its ability to inhibit copper-induced oxidation of low-density lipoprotein in vitro.
Plasma HDL concentrations did not change considerably after 6 months of therapy. However, stable increases of PON-1 activities were observed throughout the same period (p<0.03). The increases were more obvious when related to HDL or apolipoprotein AI concentrations. HDL total antioxidative capacity significantly improved 6 months after the initiation of anti-TNF therapy (p = 0.015). The initial improvement of PON-1 activity paralleled a decrease in the inflammatory status, whereas specific TNF blockade was likely to be responsible for the long-term effects.
Anti-TNF therapy with infliximab has beneficial effects on lipids through changes in HDL antioxidative capacity, which might be clinically relevant and contribute to the reported protective effect of anti-TNF on cardiovascular morbidity in RA. This emphasises the importance of HDL antiatherogenic capacity for cardiovascular risk in chronic inflammatory conditions.
在类风湿关节炎(RA)等炎症状态下,高密度脂蛋白(HDL)的抗动脉粥样硬化功能似乎会减弱。本研究旨在探讨肿瘤坏死因子(TNF)抑制对RA患者HDL抗氧化能力的影响。
在45例RA患者接受抗TNF治疗前及治疗6个月期间,检测其血脂和对氧磷酶(PON - 1)活性。此外,分离HDL并检测其在体外抑制铜诱导的低密度脂蛋白氧化的能力。
治疗6个月后血浆HDL浓度变化不大。然而,在同一时期观察到PON - 1活性持续稳定升高(p<0.03)。与HDL或载脂蛋白AI浓度相关时,升高更为明显。抗TNF治疗开始6个月后,HDL的总抗氧化能力显著提高(p = 0.015)。PON - 1活性的最初改善与炎症状态的降低平行,而特异性TNF阻断可能是长期效应的原因。
英夫利昔单抗抗TNF治疗通过改变HDL抗氧化能力对血脂产生有益影响,这可能具有临床相关性,并有助于报道的抗TNF对RA患者心血管疾病发病率的保护作用。这强调了HDL抗动脉粥样硬化能力在慢性炎症状态下对心血管风险的重要性。