Ongrádi J, Hadden J W, Bertók L, Specter S, Nelson R, Friedman H
Mikrobiológiai Intézet, Semmelweis Orvostudományi Egyetem, Budapest.
Orv Hetil. 1995 Mar 19;136(12):653-9.
Restoration of immune functions through promoting cell cycle might delay acquired immunodeficiency syndrome development. Therefore, stimulation of peripheral lymphocytes of human immunodeficiency virus-1 infected patients in successive clinical stages was studied by phytohaemagglutinin and other stimulants. In vitro blastogenesis was quantitated by 3H-thymidine uptake. Stimulation by phytohaemagglutinin decreased in patients with AIDS related complex to 63.1%, with AIDS to 13.6% of control values. Small amount of recombinant interleukin-2 or indomethacin solely not promoting lymphocytes, increased response to phytohaemagglutinin minimally. Alone ineffective methyl-ester and methyl-phosphonate inosine derivatives augmented phytohaemagglutinin-response of controls and patients with AIDS related complex by approx. 1.5-fold, but the effect in the case of AIDS patients was minimal. Radio-detoxified endotoxin alone or in combination with phytohaemagglutinin stimulated lymphocytes of both controls and patients with AIDS related complex slightly. Lymphocyte stimulation of patients with AIDS related complex was augmented in concentration-dependent manner, and by synergic effect it approached phytohaemagglutinin-stimulated blastogenesis of controls. Anergy due to human immunodeficiency virus-1 infection damages synchronisation of secondary messenger systems induced on cell surface receptors, therefore their selective influence by recombinant interleukin-2 or indomethacin is less efficient. Inosine derivatives promote cell cycle by inhibiting cyclic adenosine 3',5'-monophosphate production. In the early stage of virus infection, radio-detoxified endotoxin might bind to receptors of immature T cells and facilitate cell cycle through cyclic guanosine 3',5'-monophosphate stimulation. The clinical trials of radio-detoxified endotoxin (Tolerin) have already been launched.
通过促进细胞周期来恢复免疫功能可能会延缓获得性免疫缺陷综合征的发展。因此，研究人员使用植物血凝素和其他刺激剂对处于连续临床阶段的人类免疫缺陷病毒1型感染患者的外周淋巴细胞进行了刺激研究。通过³H-胸腺嘧啶核苷摄取对体外细胞增殖进行定量分析。植物血凝素对艾滋病相关综合征患者的刺激作用降至对照值的63.1%，对艾滋病患者则降至13.6%。单独使用少量重组白细胞介素-2或吲哚美辛对淋巴细胞促进作用不大，对植物血凝素的反应仅有轻微增加。单独无效的肌苷甲酯和肌苷甲基膦酸酯衍生物可使对照者和艾滋病相关综合征患者对植物血凝素的反应增强约1.5倍，但对艾滋病患者的效果甚微。单独使用或与植物血凝素联合使用的放射性解毒内毒素对对照者和艾滋病相关综合征患者的淋巴细胞均有轻微刺激作用。艾滋病相关综合征患者的淋巴细胞刺激作用呈浓度依赖性增强，通过协同作用，其接近植物血凝素刺激的对照者细胞增殖水平。人类免疫缺陷病毒1型感染导致的无反应性损害了细胞表面受体诱导的第二信使系统的同步性，因此重组白细胞介素-2或吲哚美辛对其的选择性影响效率较低。肌苷衍生物通过抑制环磷酸腺苷的产生来促进细胞周期。在病毒感染早期，放射性解毒内毒素可能与未成熟T细胞的受体结合，并通过刺激环磷酸鸟苷来促进细胞周期。放射性解毒内毒素（托莱林）的临床试验已经启动。
