Waagsbø Bjørn, Svardal Asbjørn, Ueland Thor, Landrø Linn, Øktedalen Olav, Berge Rolf K, Flo Trude H, Aukrust Pål, Damås Jan K
Department of Cancer Research and Molecular Medicine, Centre of Molecular Inflammation Research, NTNU, Trondheim, Norway.
Department of Infectious Diseases, St Olav's Hospital, Trondheim, Norway.
Eur J Clin Invest. 2016 May;46(5):408-17. doi: 10.1111/eci.12609. Epub 2016 Mar 7.
Carnitine plays an essential role in fatty acid metabolism, exerts substantial antioxidant action and regulates immune functions. We hypothesized that a disturbed carnitine metabolism could be involved in progression of HIV infection.
Plasma levels of L-carnitine, its precursors, and short-, medium- and long-chain acylcarnitines were analysed with HPLC/mass spectrometry in HIV-infected patients with various disease severities including patients who acquired Mycobacterium avium complex (MAC) infection. In vitro, we examined the MAC-purified protein derivate (PPD)-induced release of TNF-α and IFN-γ in peripheral blood mononuclear cells (PBMCs) from patients with either high or low plasma levels of acylcarnitines.
Plasma levels of the short-chain (e.g. propionyl-carnitine) and medium-chain (e.g. octanoyl-carnitine) acylcarnitines were reduced in patients with advanced HIV infection. These acylcarnitines gradually decreased in rapid progressors, while minimal changes were observed in the nonprogressors. Plasma levels of propionyl-carnitine and octanoyl-carnitine significantly increased during antiretroviral therapy (ART). However, ART did not restore levels to those observed in healthy controls. Depletion of propionyl-carnitine and octanoyl-carnitine was observed prior to MAC infection, and the release of TNF-α and IFN-γ from PBMC was decreased after stimulation with MAC-PPD in samples from HIV-infected patients with low levels of propionyl-carnitine or octanoyl-carnitine.
Our findings suggest an association between disturbed acylcarnitine metabolism, immune dysregulation and disease progression in HIV-infected patients. Low levels of propionyl-carnitine and octanoyl-carnitine were associated with increased susceptibility to MAC infection in HIV patients with advanced disease.
肉碱在脂肪酸代谢中起关键作用，具有显著的抗氧化作用并调节免疫功能。我们推测肉碱代谢紊乱可能与HIV感染的进展有关。
采用高效液相色谱/质谱法分析不同疾病严重程度的HIV感染患者（包括获得鸟分枝杆菌复合体[MAC]感染的患者）血浆中左旋肉碱及其前体以及短链、中链和长链酰基肉碱的水平。在体外，我们检测了血浆酰基肉碱水平高或低的患者外周血单个核细胞（PBMC）中MAC纯化蛋白衍生物（PPD）诱导的肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）释放情况。
晚期HIV感染患者血浆中的短链（如丙酰肉碱）和中链（如辛酰肉碱）酰基肉碱水平降低。这些酰基肉碱在快速进展者中逐渐下降，而在无进展者中变化极小。抗逆转录病毒治疗（ART）期间丙酰肉碱和辛酰肉碱的血浆水平显著升高。然而，ART并未使这些水平恢复到健康对照者的水平。在MAC感染之前就观察到丙酰肉碱和辛酰肉碱的消耗，并且在丙酰肉碱或辛酰肉碱水平低的HIV感染患者样本中，用MAC-PPD刺激后PBMC释放的TNF-α和IFN-γ减少。
我们的研究结果表明，HIV感染患者酰基肉碱代谢紊乱、免疫失调与疾病进展之间存在关联。丙酰肉碱和辛酰肉碱水平低与晚期HIV疾病患者对MAC感染的易感性增加有关。
