Production of the Cytokines by Blood Leukocytes, Activated with Cycloferon.

Mark M. Mendelenko, Janna N. Kravchenko, Karina V. Agadjanyan, Alexandr I. Kravchenko
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Abstract

Our investigation is an attempt to confirm the probability to use the cycloferon for the extracorporeal immunopharmacotherapy. For this aim the leukocytes, obtained from 5 ml of venous blood of 17 healthy individuals, were stimulated by different doses of cycloferon during 1 h and after 24 h we determined interferon-alpha (IFN-alpha) concentration, tumor-necrosis factor-alpha (TNF-alpha), intreleukin-4 (IL-4) in the supernatant of stimulated and intact cells. Obtained results suggest that incubation of the blood leukocytes with cycloferon lead to the evident increase of IFN-alpha production. Dose-dependent effect of the stimulation is observed in the range of the cycloferon concentrations from 50 mg/l to 200 mg/l. Cycloferon poorly induces IFN-alpha production by leukocytes (50-150 ng/l) in comparison with phytohemagglutinin and other non-specific or bacterial stimulators. However, such quantity of IFN-alpha may be adequate to stimulate immune response, if the patient is reinfused by large amount of the autologous leukocytes, activated by cycloferon, isolated from 100-400 ml blood. The influence of cycloferon is less evident in the production of TNF-alpha, IFN-gamma and IL-4 by leukocytes at the range of the studied doses. It should be noted that the individual peculiarities of donor leukocyte reaction may be seen in response to the cycloferon. Obtained results suggest the principal possibility to use autologous leukocytes extracorporeally activated by IFN inductors for the immunotherapy.

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由环铁激活的血液白细胞产生细胞因子。
本研究旨在探讨环铁素用于体外免疫药物治疗的可能性。为此,取17例健康人5 ml静脉血,用不同剂量的环铁刺激1 h, 24 h后测定刺激细胞和完整细胞上清中的干扰素- α (ifn - α)、肿瘤坏死因子- α (tnf - α)、白细胞介素-4 (IL-4)的浓度。结果表明,血液白细胞与环铁素孵育导致ifn - α的产生明显增加。在环铁浓度为50mg /l ~ 200mg /l范围内观察到刺激的剂量依赖性效应。与植物血凝素和其他非特异性或细菌刺激剂相比,Cycloferon诱导白细胞产生ifn - α的能力较差(50-150 ng/l)。然而,如果从100- 400ml血液中分离出大量经环铁活化的自体白细胞再输注患者,这种数量的ifn - α可能足以刺激免疫反应。在研究剂量范围内,环铁素对白细胞产生tnf - α、ifn - γ和IL-4的影响不太明显。应该注意的是,供体白细胞反应的个体特性可以在对环铁离子的反应中看到。所获得的结果表明,利用IFN诱导剂体外激活的自体白细胞进行免疫治疗的主要可能性。
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