The role of IL-1β in nicotine-induced immunosuppression and neuroimmune communication.
The role of IL-1β in nicotine-induced immunosuppression and neuroimmune communication.
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DOI：
10.1007/s11481-011-9284-5
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Sopori ML
中科院分区：
文献类型：
--
作者：
Razani-Boroujerdi S;Langley RJ;Singh SP;Pena-Philippides JC;Rir-sima-ah J;Gundavarapu S;Mishra NC;Sopori ML
尽管在脓毒症期间许多炎性细胞因子增加，但旨在下调这些介质的临床试验并未改善结果。这些自相矛盾的结果归因于通常在促炎反应之后的“耐受”阶段的丧失。慢性尼古丁（NT）可抑制适应性和先天性免疫反应，其作用部分由脑内的烟碱乙酰胆碱受体介导，但神经免疫通讯机制尚不清楚。在这里，我们提供的证据表明，在大鼠和小鼠中，NT最初增加脑中的IL-1β，但在慢性暴露的1-2周内表达下调，并且动物对促炎性/致热原刺激具有抗性。为了检验NT、IL-1β和免疫抑制之间的关系，我们假设NT在脑中诱导IL-1β，并且其持续存在产生免疫“耐受”。事实上，与野生型C57 BL/6小鼠不同，慢性NT未能诱导IL-1β受体敲除小鼠的免疫抑制或IL-1β表达下调。此外，虽然LEW大鼠脑室内急性给予IL-1β可激活脾脏中的Fyn和蛋白酪氨酸激酶活性，但长期给予低水平的IL-1β可逐渐减少给药动物的致热反应和T细胞增殖反应。因此，IL-1β可能在CNS对炎症的感知和免疫“耐受”状态的诱导中发挥关键作用。NT的免疫抑制作用可能至少部分是通过影响脑内IL-1β而实现的。这代表了神经免疫通讯的一种新机制。
Although a number of inflammatory cytokines are increased during sepsis, the clinical trials aimed at down-regulating these mediators have not improved the outcome. These paradoxical results are attributed to loss of the “tolerance” phase that normally follows the proinflammatory response. Chronic nicotine (NT) suppresses both adaptive and innate immune responses, and the effects are partly mediated by the nicotinic acetylcholine receptors in the brain; however, the mechanism of neuroimmune communication is not clear. Here, we present evidence that, in rats and mice, NT initially increases IL-1β in the brain, but the expression is downregulated within 1–2 wk of chronic exposure, and the animals become resistant to proinflammatory/pyrogenic stimuli. To examine the relationship between NT, IL-1β, and immunosuppression, we hypothesized that NT induces IL-1β in the brain, and its constant presence produces immunological “tolerance.” Indeed, unlike wild-type C57BL/6 mice, chronic NT failed to induce immunosuppression or downregulation of IL-1β expression in IL-1β-receptor knockout mice. Moreover, while acute intracerebroventricular administration of IL-1β in LEW rats activated Fyn and protein tyrosine kinase activities in the spleen, chronic administration of low levels of IL-1β progressively diminished the pyrogenic and T cell proliferative responses of treated animals. Thus, IL-1β may play a critical role in the perception of inflammation by the CNS and the induction of an immunologic “tolerant” state. Moreover, the immunosuppressive effects of NT might be at least partly mediated through its effects on the brain IL-1β. This represents a novel mechanism for neuroimmune communication.
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影响因子：
4.3
作者：
Razani-Boroujerdi, S;Singh, SP;Sopori, ML
通讯作者：
Sopori, ML
DOI：
10.1111/j.1749-6632.1998.tb08310.x
发表时间：
1998-01-01
期刊：
MOLECULAR MECHANISMS OF FEVER
影响因子：
--
作者：
Kozak, W;Kluger, MJ;Zheng, H
通讯作者：
Zheng, H
DOI：
10.1016/j.injury.2007.10.003
发表时间：
2007-12-01
影响因子：
2.5
作者：
Lenz, Andreas;Franklin, Glen A.;Cheadle, William G.
通讯作者：
Cheadle, William G.
影响因子：
4.4
作者：
Razani-Boroujerdi, Seddigheh;Boyd, R. Thomas;Sopori, Mohan L.
通讯作者：
Sopori, Mohan L.
影响因子：
38.9
作者：
Kox, WJ;Volk, T;Volk, HD
通讯作者：
Volk, HD