De Simone C, Famularo G, Tzantzoglou S, Trinchieri V, Moretti S, Sorice F
Department of Infectious Diseases, University of L'Aquila, Italy.
AIDS. 1994 May;8(5):655-60. doi: 10.1097/00002030-199405000-00012.
Reduced levels of serum carnitines (3-hydroxy-4-N-trimethyl-ammonio-butanoate) are found in most patients treated with zidovudine. However, since serum carnitines do not strictly reflect cellular concentrations we examined whether a carnitine depletion could be found in peripheral blood mononuclear cells (PBMC) from AIDS patients with normal serum carnitine levels. In addition, we explored whether it was possible to relate the host's immunoreactivity to the content of carnitine in PBMC and whether carnitine levels can be corrected by oral supplementation of L-carnitine.
Immunopharmacologic study.
Twenty male patients with advanced AIDS (Centers for Disease Control and Prevention stage IVCI) and normal serum levels of carnitines were enrolled. Patients were randomly assigned to receive either L-carnitine (6 g/day) or placebo for 2 weeks. At baseline and at the end of the trial, we measured carnitines in both sera and PBMC, serum triglycerides, CD4 cell counts, and the frequency of cells entering the S and G2-M phases of cell cycle following mitogen stimulation.
Concentrations of total carnitine in PBMC from AIDS patients was lower than in healthy controls. A significant trend towards the restoration of appropriate intracellular carnitine levels was found in patients treated with high-dose L-carnitine and was associated with an increased frequency of S and G2-M cells following mitogen stimulation. Furthermore, at the end of the trial we found a strong reduction in serum triglycerides in the L-carnitine group compared with baseline levels.
Our data indicate that carnitine deficiency occurs in PBMC from patients with advanced AIDS, despite normal serum concentrations. The increase in cellular carnitine content strongly improved lymphocyte proliferative responsiveness to mitogens. Because carnitine status is an important contributing factor to immune function in patients with advanced AIDS, we therefore believe that L-carnitine supplementation could have a role as a complementary therapy for HIV-infected individuals.
在大多数接受齐多夫定治疗的患者中发现血清肉碱（3-羟基-4-N-三甲基铵丁酸酯）水平降低。然而，由于血清肉碱并不能严格反映细胞内浓度，我们研究了血清肉碱水平正常的艾滋病患者外周血单个核细胞（PBMC）中是否存在肉碱缺乏。此外，我们探讨了宿主免疫反应性与PBMC中肉碱含量之间是否存在关联，以及口服补充左旋肉碱是否可以纠正肉碱水平。
免疫药理学研究。
招募了20名晚期艾滋病男性患者（疾病控制和预防中心IVCI期），其血清肉碱水平正常。患者被随机分配接受左旋肉碱（6克/天）或安慰剂治疗2周。在基线和试验结束时，我们测量了血清和PBMC中的肉碱、血清甘油三酯、CD4细胞计数以及丝裂原刺激后进入细胞周期S期和G2-M期的细胞频率。
艾滋病患者PBMC中总肉碱浓度低于健康对照组。在接受高剂量左旋肉碱治疗的患者中发现了细胞内肉碱水平恢复到适当水平的显著趋势，并且与丝裂原刺激后S期和G2-M期细胞频率增加有关。此外，在试验结束时，我们发现左旋肉碱组的血清甘油三酯与基线水平相比大幅降低。
我们的数据表明，尽管血清浓度正常，但晚期艾滋病患者的PBMC中存在肉碱缺乏。细胞内肉碱含量的增加显著改善了淋巴细胞对丝裂原的增殖反应性。由于肉碱状态是晚期艾滋病患者免疫功能的一个重要影响因素，因此我们认为补充左旋肉碱可能作为HIV感染者的辅助治疗方法。
