Biocenter, Innsbruck Medical University, Austria.
Pharmacol Res. 2009 Dec;60(6):508-14. doi: 10.1016/j.phrs.2009.07.009. Epub 2009 Aug 3.
Higher concentrations of inflammation and immune activation markers as well as the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are associated with an increased cardiovascular risk. In vitro, parallel formation of ADMA and macrophage marker neopterin was found in stimulated human peripheral blood mononuclear cells.
In 112 HIV-1 infected patients, concentrations of ADMA, SDMA and arginine were compared to C-reactive protein and neopterin concentrations before they were referred to antiretroviral therapy. Disease activity was determined by viral load (qPCR), CD4(+) cell counts (FACS) and neopterin concentrations in plasma and urine (HPLC and ELISA). Additionally, concentrations of lipids were determined.
HIV-1 infected patients presented with increased neopterin, ADMA and SDMA concentrations, whereas CD4(+) counts and arginine and plasma lipid concentrations were low. ADMA and SDMA concentrations significantly correlated with markers of immune activation, but not with plasma lipids.
Results of this study indicate that increased ADMA and SDMA production may be related to an increased activity of immune activation pathways.
炎症和免疫激活标志物以及内源性一氧化氮合酶抑制剂不对称二甲基精氨酸(ADMA)浓度升高与心血管风险增加相关。在体外,刺激人外周血单核细胞中发现 ADMA 和巨噬细胞标志物新蝶呤平行形成。
在 112 名 HIV-1 感染患者中,在将他们转介接受抗逆转录病毒治疗之前,比较了 ADMA、SDMA 和精氨酸与 C-反应蛋白和新蝶呤浓度。通过病毒载量(qPCR)、CD4(+) 细胞计数(FACS)和血浆及尿液中的新蝶呤浓度(HPLC 和 ELISA)来确定疾病活动度。此外,还测定了脂质浓度。
HIV-1 感染患者的新蝶呤、ADMA 和 SDMA 浓度升高,而 CD4(+) 计数和精氨酸以及血浆脂质浓度较低。ADMA 和 SDMA 浓度与免疫激活标志物显著相关,但与血浆脂质无关。
本研究结果表明,ADMA 和 SDMA 产生增加可能与免疫激活途径活性增加有关。