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通过N-乙酰半胱氨酸释放细胞因子实现辐射防护

[Radiation protection through cytokine release by N-acetylcysteine].

作者信息

Baier J E, Neumann H A, Moeller T, Kissler M, Borchardt D, Ricken D

机构信息

Medizinische Klinik der Ruhr-Universität Bochum.

出版信息

Strahlenther Onkol. 1996 Feb;172(2):91-8.

PMID:8669050
Abstract

BACKGROUND

Interleukin-1, tumornecrosisfactor-alpha and interferon-gamma endogenously provide protection of the hematopoietic system against radiation. Thiols have already been used successfully as radioprotective agents. In this study the effect von N-acetylcysteine (NAC) on the release of interleukin-1 alpha and beta (IL-1), interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and tumornecrosisfactor-alpha (TNF-alpha) was assessed in an in vitro assay.

PATIENTS AND METHODS

Whole blood samples from 8 healthy volunteers were stimulated with 7.5 micrograms/ml PHA. NAC was added at concentrations of 0.6, 6, 12 and 24 mmol/l. Subsequently the samples were irradiated with a dose of 18 Gy according to preceding validation experiments.

RESULTS

IL-1 alpha, IL-1 beta b and IL-2: In comparison to stimulation and radiation alone the addition of 0.6 and 6 mmol/l, with IL-2 also 12 mmol/l, NAC resulted in a significant increase of the cytokine-concentrations. The highest concentration of 24 mmol/l NAC, however, resulted in a decrease beyond control levels. IFN-gamma and TNF-alpha: Until 12 mmol/l NAC no changes were observed. 24 mmol/l NAC resulted in a significant decrease, too.

CONCLUSION

N-acetylcysteine is capable to co-stimulate radioprotective cytokines like IL-1 alpha and IL-1 beta and to enhance IL-2 in vitro, whereas higher doses result in a suppression.

摘要

背景

白细胞介素 -1、肿瘤坏死因子 -α和干扰素 -γ可内源性地保护造血系统免受辐射。硫醇已成功用作辐射防护剂。在本研究中,通过体外试验评估了N - 乙酰半胱氨酸(NAC)对白细胞介素 -1α和β(IL -1)、白细胞介素 -2(IL -2)、干扰素 -γ(IFN -γ)和肿瘤坏死因子 -α(TNF -α)释放的影响。

患者和方法

用7.5微克/毫升的PHA刺激8名健康志愿者的全血样本。加入浓度为0.6、6、12和24毫摩尔/升的NAC。随后根据先前的验证实验,用18戈瑞的剂量对样本进行辐照。

结果

IL -1α、IL -1β和IL -2:与单独刺激和辐射相比,加入0.6和6毫摩尔/升,对于IL -2还加入12毫摩尔/升的NAC后,细胞因子浓度显著增加。然而,24毫摩尔/升的NAC最高浓度导致浓度降至对照水平以下。IFN -γ和TNF -α:直到12毫摩尔/升的NAC,未观察到变化。24毫摩尔/升的NAC也导致显著下降。

结论

N - 乙酰半胱氨酸能够在体外共同刺激像IL -1α和IL -1β这样的辐射防护细胞因子并增强IL -2,而更高剂量则导致抑制。

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