Nair M P, Kronfol Z A, Schwartz S A
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
Clin Immunol Immunopathol. 1990 Mar;54(3):395-409. doi: 10.1016/0090-1229(90)90053-s.
The in vitro effects of the recreational drugs, ethanol (EtOH) and nicotine, on natural killer (NK) antibody-dependent cellular cytotoxic (ADCC) and lymphokine-activated killer (LAK) cell activities on normal lymphocytes were investigated. Lymphocytes precultured with EtOH at concentrations of 0.4 and 0.6% (v/v) produced significant suppression of NK and ADCC activities. In target-binding assays, EtOH decreased the target-binding capacity of effector cells. EtOH also inhibited the activities of Percoll-separated, NK-enriched large granular lymphocytes. EtOH-induced inhibition of NK activity could be reversed by incubating lymphocytes for 1 hr with interferon. The generation and lytic capacity of LAK cells was also significantly depressed by EtOH when added at the initiation of culture. Nicotine at concentrations of 5 and 10 micrograms/ml, when added directly to mixtures of effector and target cells, produced significant inhibition of NK activity. Nicotine (2 micrograms/ml) and EtOH (0.01, 0.1, and 0.2%) at noninhibitory concentrations when added separately, showed significant suppression of NK activity when used in combination. Pretreatment of target cells with either EtOH or nicotine for 4 hr did not affect cytotoxic activity. Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or nicotine showed normal 51Cr release and their viability was comparable to that of untreated control cells. These studies demonstrate that EtOH and nicotine have significant immunomodulatory effects on the cytotoxic activities of human lymphocytes which may be of clinical relevance.
研究了娱乐性药物乙醇（EtOH）和尼古丁对正常淋巴细胞的自然杀伤（NK）抗体依赖性细胞毒性（ADCC）和淋巴因子激活的杀伤（LAK）细胞活性的体外影响。用浓度为0.4%和0.6%（v/v）的EtOH预培养的淋巴细胞对NK和ADCC活性产生了显著抑制。在靶细胞结合试验中，EtOH降低了效应细胞的靶细胞结合能力。EtOH还抑制了经Percoll分离的富含NK的大颗粒淋巴细胞的活性。通过用干扰素孵育淋巴细胞1小时，可逆转EtOH诱导的NK活性抑制。当在培养开始时加入EtOH时，LAK细胞的生成和裂解能力也受到显著抑制。当直接添加到效应细胞和靶细胞的混合物中时，浓度为5和10微克/毫升的尼古丁对NK活性产生了显著抑制。当分别以非抑制浓度添加尼古丁（2微克/毫升）和EtOH（0.01%、0.1%和0.2%）时，联合使用时对NK活性有显著抑制作用。用EtOH或尼古丁预处理靶细胞4小时不影响细胞毒性活性。细胞毒性的抑制也不是由于效应细胞的直接毒性，因为用EtOH或尼古丁处理的淋巴细胞显示出正常的51Cr释放，并且它们的活力与未处理的对照细胞相当。这些研究表明，EtOH和尼古丁对人淋巴细胞的细胞毒性活性具有显著的免疫调节作用，这可能具有临床相关性。
