Soderberg L S, Barnett J B
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock.
J Leukoc Biol. 1995 Jan;57(1):135-40. doi: 10.1002/jlb.57.1.135.
Abuse of nitrite inhalants is common among male homosexuals and a history of abuse has been correlated with seropositivity to HIV and with the incidence of Kaposi's sarcoma among AIDS patients. The present study shows that inhalation exposure of mice to 900 ppm isobutyl nitrite for 45 min/day for 14 days compromised macrophage tumoricidal activity by up to 40% and it remained compromised for at least 7 days after terminating exposures. The inhalation exposures did not affect tumor cell binding but did inhibit inducible nitric oxide (NO zero). The NO zero synthase inhibitor NG-methyl-L-arginine totally inhibited both NO zero production and cytotoxicity, suggesting that reductions in NO zero due to inhalant exposure may be responsible for the reduced cytotoxic activity. Exposure to the inhalant increased constitutive production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha has been reported to stimulate the replication of HIV and the proliferation of Kaposi's sarcoma cells in vitro.
亚硝酸盐吸入剂的滥用在男性同性恋者中很常见，滥用史与HIV血清阳性以及艾滋病患者中卡波西肉瘤的发病率相关。本研究表明，小鼠每天吸入900 ppm亚硝酸异丁酯，持续45分钟，共14天，巨噬细胞的杀肿瘤活性最多降低40%，在停止暴露后至少7天仍保持降低状态。吸入暴露不影响肿瘤细胞结合，但确实抑制了诱导型一氧化氮（NO零）。NO零合酶抑制剂NG-甲基-L-精氨酸完全抑制了NO零的产生和细胞毒性，这表明吸入剂暴露导致的NO零减少可能是细胞毒性活性降低的原因。暴露于吸入剂会增加肿瘤坏死因子-α（TNF-α）的组成性产生。据报道，TNF-α在体外可刺激HIV的复制和卡波西肉瘤细胞的增殖。
