Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats
Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats
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DOI：
10.1016/j.bcp.2011.02.004
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发表时间：
2011-05-01
影响因子：
5.8
通讯作者：
Pentel, P. R.
中科院分区：
文献类型：
--
作者：
Pravetoni, M.;Keyler, D. E.;Pentel, P. R.
尼古丁疫苗药理学的临床前模型依赖于静脉注射。或 s.c.尼古丁的管理。使用香烟烟雾吸入的模型可能更准确地模拟吸烟者的尼古丁暴露。使用两种香烟烟雾暴露模型在大鼠中检查尼古丁疫苗的效果：仅鼻暴露（NSE）10分钟，产生的血清尼古丁水平相当于吸烟者吸1支烟所产生的尼古丁增加量；以及全身暴露（WBE）2小时，产生的血清尼古丁水平与经常中午吸烟的水平相似。吸烟 10 分钟前接种 NSE 可使尼古丁向大脑的分布减少 90%，这与静脉注射尼古丁的效果相当。吸烟 WBE 前 2 小时接种疫苗可使尼古丁向大脑的分布减少 35%。在 WBE 2 小时后获得的支气管肺泡灌洗 (BAL) 液中的尼古丁浓度，在接种疫苗的大鼠中增加了 230%，但在用尼古丁特异性单克隆抗体被动免疫的大鼠中也增加了，因此可能是由于抗体从血清转移而不是肺粘膜局部产生。在 BAL 液中未检测到尼古丁特异性 IgA，但血清中的滴度相当可观，为 IgG 滴度的 21-25%，可能有助于疫苗功效。当尼古丁通过吸入香烟烟雾输送时，疫苗接种和被动免疫均可有效减少尼古丁向大脑的分布。这些数据验证了先前在啮齿动物中使用静脉注射尼古丁疫苗获得的结果。或 s.c.尼古丁剂量，并为研究香烟烟雾吸入所特有的尼古丁暴露方面提供定量方法。由爱思唯尔公司出版
Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 min nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a 2 h whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular mid-day smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 h smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 h WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21-25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation. Published by Elsevier Inc.