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滥用药物导致外周免疫反应和中枢神经胶质细胞活动的颠覆:聚焦新型治疗方法。

Drugs of Abuse Induced-Subversion of the Peripheral Immune Response and Central Glial Activity: Focus on Novel Therapeutic Approaches.

作者信息

Magrone Thea, Jirillo Emilio

机构信息

Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, School of Medicine, Bari, Italy.

出版信息

Endocr Metab Immune Disord Drug Targets. 2019;19(3):281-291. doi: 10.2174/1871530319666181129104329.

Abstract

BACKGROUND

Drugs of abuse affect both central nervous system (CNS) and peripheral immune function. Besides the involvement of dopamine and glutamate systems, chronic exposure to drugs of abuse alters immune homeostasis, promoting a pro-inflammatory status. At the same time, impaired peripheral immunity leads to an increased susceptibility to infections in drug abusers.

DISCUSSION

There is evidence that certain drugs, such as opioids, activate microglial cells and astrocytes which, in turn, provoke central neuroinflammation. Particularly, opioids bind the Toll-like receptor (TLR)-4 with increased expression of nuclear factor kappa-light-chain-enhancer of activated B cells and release of pro-inflammatory cytokines. Peripheral mediators released by immune cells also contribute to aggravate central neuroinflammation.

CONCLUSION

These are based either on the inhibition of TLR-4 activation by drugs of abuse or on the correction of dopamine and glutamate pathways. Finally, a hypothetic nutraceutical intervention with polyphenols in view of their anti-inflammatory and anti-oxidant properties will be outlined as an adjuvant treatment for drugs of abuse-related disorders.

摘要

背景

滥用药物会影响中枢神经系统(CNS)和外周免疫功能。除了多巴胺和谷氨酸系统的参与外,长期接触滥用药物会改变免疫稳态,促进促炎状态。同时,外周免疫功能受损会导致药物滥用者对感染的易感性增加。

讨论

有证据表明,某些药物,如阿片类药物,会激活小胶质细胞和星形胶质细胞,进而引发中枢神经炎症。特别是,阿片类药物与Toll样受体(TLR)-4结合,增加活化B细胞核因子κ轻链增强子的表达并释放促炎细胞因子。免疫细胞释放的外周介质也有助于加重中枢神经炎症。

结论

这些措施要么基于滥用药物对TLR-4激活的抑制,要么基于多巴胺和谷氨酸途径的校正。最后,鉴于多酚的抗炎和抗氧化特性,将概述一种假设的多酚营养干预措施,作为滥用药物相关疾病的辅助治疗方法。

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