苯二氮平類藥物之免疫毒性

免疫功能的異常和許多病變相關，例如傳染病、癌症和過敏性疾病等，許多影響中樞的藥物包含鴉片、安非他命和大麻等，皆具有免疫毒性。本文針對苯二氮平類藥物的免疫毒性進行文獻回顧。證據顯示苯二氮平類藥物對免疫細胞的功能和活性有顯著的作用，包括抑制作用和促進作用。此類藥物的中樞活性係透過中樞受體引起，除了中樞受體，哺乳類細胞表現第二型受體：周邊受體，此受體和藥物對免疫系統的作用有關。在各類免疫細胞中，吞噬細胞對苯二氮平類藥物最為敏感，只需nM濃度即會影響其吞噬、活化和增生的功能。相對於此，藥物影響T淋巴球的證據較不充分，且藥物的有效濃度為μM濃度。除了以細胞的實驗外，大量的動物實驗報告指出苯二氮平類藥物的活體免疫毒性，例如暴露於藥物的動物，其抵抗病原的防禦力明顯降低。苯二氮平的另一項免疫毒性為對免疫系統發育的毒性，子宮內暴露於藥物會導致出生子代大鼠免疫機能的損傷。胚胎期藥物暴露的有效期間和免疫細胞開始表現苯二氮平周邊受體的時期吻合，顯示周邊受體和此免疫毒性的密切關聯性。基於此點，懷孕期動物使用苯二氮平類藥物的危險性需加以審慎評估。文獻也指出抗焦慮的苯二氮平類藥物具有保護動物體免於壓力所引起的免疫抑制效應，此活性係經由中樞受體。綜合上述，免疫系統是苯二氮平類藥物的敏感標的之一，苯二氮平類藥物周邊受體和此類藥物抑制免疫系統防禦感染的作用密切相關。此外，具抗焦慮活性的苯二氮平類藥物能解除壓力引起的免疫抑制。根據這些結果，有關苯二氮平類藥物和受體的生理功能和藥理毒理作用值得進一步研究。

關鍵字

苯二氮平；免疫毒性；周邊受體；壓力

並列摘要

Alterations in the immune functions are associated with the pathophysiology of many diseases, such as infection, cancer and allergy. Psychoactive drugs, including opioids, amphetamines and marijuana, have been documented to cause immunotoxicity. This paper reviews the literature reports on the immunotoxicity of benzodiazepines (BDZ). Ample evidence indicates that BDZ exhibit profound effects on the function and activities of various immune cells. Benzodiazepines induce pharmacological effects on the central nervous system via the binding to the central BDZ receptors. In addition to the central receptor, mammalian cells express the peripheral BDZ receptors that play a pivotal role in the immunomodulatory effects of BDZ. Considerable evidence indicates a broad spectrum of immunotoxicity induced by BDZ. Among the various immune cells, phagocytes are the most sensitive to BDZ, in which nM of BDZ effectively modulate their phagocytosis, activation and proliferation. On the other hand, evidence pertaining to the effects of BDZ on T cells is limited, and the effective drug concentrations are in the 1.tM range. Animal studies also indicate that BDZ are immunosuppressive in vivo. For example, the capability of BDZ-exposed animals to defense pathogenic microorganisms is impaired. Another important feature of BDZ-induced immunotoxicity is the developmental toxicity associated with prenatal exposure of BDZ. In utero exposure to BDZ results in the impairment of immune cell functions. The period of prenatal exposure that affects the offspring immune functiona correlates with the expression of the peripheral BDZ receptors by the immunocytes, suggesting a potential linkage between the receptor and the immunnotoxicity. In light of this evidence, the risk of using BDZ during pregnancy needs to be carefully considered. Furthermore, sme evidence in the literature suggests that anxiolytic BDZ may protect the individual from stress-induced immunosuppression. Together the available literature evidence clear indicates that the immune system is a sensitive target for BDZ. The physiological and pharmacological role of BDZ receptors warrants further investigation.

並列關鍵字

benzodiazepine ； immunotoxicity ； peripheral receptor ； stress

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苯二氮平類藥物之免疫毒性

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