Influence of the course of brain inflammation on the endogenous IL-1β/IL-1Ra balance in the model of brain delayed-type hypersensitivity response to bacillus Calmette-Guerin in Lewis rats
Influence of the course of brain inflammation on the endogenous IL-1β/IL-1Ra balance in the model of brain delayed-type hypersensitivity response to bacillus Calmette-Guerin in Lewis rats
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DOI：
10.1016/j.jneuroim.2003.12.005
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发表时间：
2004-04-01
影响因子：
3.3
通讯作者：
Lestage, J
中科院分区：
文献类型：
--
作者：
Palin, K;Verrier, D;Lestage, J
白细胞介素-1β (IL-1beta) 是外周和大脑急性和慢性炎症性疾病发病机制中的关键角色。其作用受白介素 1 受体拮抗剂 (IL-1Ra) 调节，IL-1Ra 是 IL-1 受体的特异性内源性拮抗剂。已知 IL-1Ra 和 IL-1β 局部浓度之间的比率会影响外周许多炎症和自身免疫性疾病的发生和进展。为了确定大脑中是否也是这种情况，通过 ELISA 在 Lewis 大鼠慢性脑炎症模型中测量了大脑和血浆中 IL-1β 和 IL-1Ra 的浓度，即海马对卡介苗 (BCG) 的迟发型超敏反应 (DTH)。脑内注射卡介苗后，脑内IL-1迅速增加，1周后恢复到基线浓度，而IL-1Ra随着时间的推移逐渐增加，并在脑内注射卡介苗后的最后两周内保持升高状态。外周 BCG 攻击后，大脑 BCG 部位的脑部 IL-1 增加，并在 12 天后达到峰值，然后在攻击后第 16 天下降。大脑 IL-1Ra 在攻击后第一天保持升高，然后从攻击后第 12 天开始下降。在 IL-1β 和 IL-1Ra 的血浆浓度中观察到相同的时间变化。攻击后第 3 天至第 12 天，IL-1β/IL-1Ra 比率明显增加，可能与脑内注射部位外周炎症细胞的侵袭有关。除了表明炎症过程会改变大脑 IL-1β/IL-1Ra 比率之外，这些发现还指出了监测血浆 IL-1β/IL-1Ra 比率对于预测脑炎症过程的重要性。 (C) 2004 Elsevier B.V. 保留所有权利。
Interleukin-1beta (IL-1beta) is a key player in the pathogenesis of acute and chronic inflammatory diseases at the periphery and in the brain. Its action is regulated by interleukin-1 receptor antagonist (IL-1Ra), the specific endogenous antagonist of IL-1 receptors. The ratio between local concentrations of IL-1Ra and IL-1beta is known to influence the initiation and progression of many inflammatory and autoimmune diseases at the periphery. In order to determine whether this is also the case in the brain, brain and plasma concentrations of IL-1beta and IL-1Ra were measured by ELISA in a model of chronic brain inflammation in Lewis rats, the hippocampal delayed-type hypersensitivity (DTH) response to bacillus Calmette-Guerin (BCG). Brain IL-1 increased rapidly after intracerebral (i.e.) injection of BCG and came back to baseline concentrations 1 week later, whereas IL-1Ra increased gradually over time and remained elevated during the last 2 weeks post-BCG intracerebral injection. Following peripheral BCG challenge, brain IL-1 increased at the site of the brain BCG and peaked 12 days later before decreasing on day 16 post-challenge. Brain IL-1Ra remained elevated during the first days post-challenge and then decreased from the 12th day post-challenge. The same temporal variations were observed in the plasma concentrations of IL-1beta and IL-1Ra. The increase in the IL-1beta/IL-1Ra ratio that was apparent from day 3 to day 12 post-challenge might be correlated with the invasion of peripheral inflammatory cells at the site of intracerebral injection. Besides showing that the course of inflammation alters the brain IL-1beta/IL-1Ra ratio, these findings point to the importance of monitoring plasma IL-1beta/IL-1Ra ratio to predict the course of brain inflammation. (C) 2004 Elsevier B.V. All rights reserved.