Lotzová E, Savary C A, Hersh E M, Khan A A, Rosenblum M
Cancer Immunol Immunother. 1984;17(2):130-4. doi: 10.1007/BF00200049.
We have investigated the effect of isobutyl nitrite on murine NK-cell antitumor-directed cytotoxicity. This agent has been suggested as one of the factors underlying immunodeficiency syndrome (AIDS) in man. We demonstrated that two injections, each of 0.25 ml isobutyl nitrite, resulted in significant depression of endogenous splenic and peripheral blood natural killer (NK) cell cytotoxicity against T-cell lymphoma, YAC-1. In addition to endogenous NK cells, activity of pyrimidinol-activated NK cells was also substantially depressed by this agent. The latter observation is of the utmost importance, since it suggests that the attempt to augment NK-cell activity (to promote resistance to infections and malignancies) could fail in patients with AIDS who are isobutyl nitrite users. Isobutyl nitrite was NK-cell-suppressive not only after in vivo administration but, most importantly, also after inhalation. This indicates that isobutyl nitrite, via its NK-cell suppressive effect, could contribute to immunodeficiency in AIDS. Studies on the mechanism of NK-cell depression by isobutyl nitrite demonstrated that the NK-cell tumor-binding properties as well as NK-cell cytotoxic potential were substantially depressed. Mixing experiments failed to reveal any regulation by suppressor cell activities. The results of these studies clearly indicate that isobutyl nitrite is an immunosuppressive agent and that its use should be avoided.
我们研究了亚硝酸异丁酯对小鼠自然杀伤（NK）细胞抗肿瘤定向细胞毒性的影响。这种物质被认为是人类免疫缺陷综合征（艾滋病）潜在的因素之一。我们证明，两次注射，每次0.25毫升亚硝酸异丁酯，会导致内源性脾和外周血自然杀伤（NK）细胞对T细胞淋巴瘤YAC-1的细胞毒性显著降低。除了内源性NK细胞外，嘧啶醇激活的NK细胞的活性也被这种物质大幅降低。后一观察结果极为重要，因为这表明，对于使用亚硝酸异丁酯的艾滋病患者，增强NK细胞活性（以促进对感染和恶性肿瘤的抵抗力）的尝试可能会失败。亚硝酸异丁酯不仅在体内给药后具有NK细胞抑制作用，而且最重要的是，吸入后也有此作用。这表明亚硝酸异丁酯通过其NK细胞抑制作用，可能导致艾滋病患者的免疫缺陷。对亚硝酸异丁酯抑制NK细胞机制的研究表明，NK细胞与肿瘤结合的特性以及NK细胞的细胞毒性潜力均大幅降低。混合实验未能揭示抑制细胞活性的任何调节作用。这些研究结果清楚地表明，亚硝酸异丁酯是一种免疫抑制剂，应避免使用。
