Marijuana and cocaine impair alveolar macrophage function and cytokine production
Marijuana and cocaine impair alveolar macrophage function and cytokine production
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DOI：
10.1164/ajrccm.156.5.9704146
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发表时间：
1997-11-01
影响因子：
24.7
通讯作者：
Roth, MD
中科院分区：
文献类型：
--
作者：
Baldwin, GC;Tashkin, DP;Roth, MD
大麻和可卡因的使用在美国呈上升趋势。虽然这些药物的肺毒性偶尔有报道，但对它们对肺微环境的影响知之甚少。我们评估了从非吸烟者和习惯性吸烟者的肺中回收的肺泡巨噬细胞（AM）的功能，无论是烟草，大麻还是快克可卡因。从吸食大麻者中回收的AM缺乏吞噬金黄色葡萄球菌的能力（p < 0.01）。来自大麻吸食者和可卡因使用者的AM在杀死细菌和肿瘤细胞的能力方面也受到严重限制（p < 0.01）。使用N-G-单甲基-L-精氨酸单乙酸酯（一氧化氮合酶抑制剂）的研究表明，来自非吸烟者和吸烟者的AM能够使用一氧化氮作为抗菌效应分子，而来自大麻和可卡因吸烟者的AM则不能。最后，来自大麻吸烟者的AM，而不是来自烟草或可卡因吸烟者的AM，在脂多糖刺激培养物时，产生的肿瘤坏死因子-α、粒细胞-巨噬细胞集落刺激因子和白细胞介素-6低于正常量。相比之下，转化生长因子-β（一种免疫抑制细胞因子）的产生在所有组中相似。这些发现表明，习惯性暴露于大麻或可卡因的肺损害AM的功能和/或细胞因子的产生。这些影响的最终结果可能是增加对传染病、癌症和艾滋病的易感性。
Use of marijuana and cocaine is on the rise in the United States. Although pulmonary toxicity from these drugs has occasionally been reported, little is known about their effects on the lung microenvironment. We evaluated the function of alveolar macrophages (AMs) recovered from the lungs of nonsmokers and habitual smokers of either tobacco, marijuana, or crack cocaine. AMs recovered from marijuana smokers were deficient in their ability to phagocytose Staphylococcus aureus (p < 0.01). AMs from marijuana smokers and from cocaine users were also severely limited in their ability to kill both bacteria and tumor cells (p < 0.01). Studies using N-G-monomethyl-L-arginine monoacetate, an inhibitor of nitric oxide synthase, suggest that AMs from nonsmokers and tobacco smokers were able to use nitric oxide as an antibacterial effector molecule, while AMs from smokers of marijuana and cocaine were not. Finally, AMs from marijuana smokers, but not from smokers of tobacco or cocaine, produced less than normal amounts of tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-6 when stimulated in culture with lipopolysaccharide. In contrast, the production of transforming growth factor-beta, an immunosuppressive cytokine, was similar in all groups. These findings indicate that habitual exposure of the lung to either marijuana or cocaine impairs the function and/or cytokine production of AMs. The ultimate outcome of these effects may be an enhanced susceptibility to infectious disease, cancer, and AIDS.