Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide
Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide
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DOI：
10.1111/j.1460-9568.2008.06549.x
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发表时间：
2008-12-01
影响因子：
3.4
通讯作者：
Dantzer, R.
中科院分区：
文献类型：
--
作者：
Konsman, J. P.;Veeneman, J.;Dantzer, R.
虽然促炎细胞因子白细胞介素-1的受体早已被认为在大脑中表达，但它们在对组织感染的急性期反应（APR）期间观察到的发热和行为抑郁中的作用仍不清楚。这可能部分是由于脑中的白细胞介素-1在外周给予细菌脂多糖（LPS）后仅数小时才具有生物活性。为了研究脑白细胞介素-1作用在温度和行为变化中的作用，以及在APR期间脑结构的激活，将白细胞介素-1受体拮抗剂（IL-1 ra; 100 μ g）在腹膜内（i. p.）LPS注射（250 μ g/kg）。腹腔注射LPS可诱导体循环以及脑室周围器官和脉络丛产生白细胞介素-1 β（IL-1 β）。脑室内（i. c. v.）腹腔注射LPS后4小时输注IL-1 ra减弱了社会交往的减少，这是疾病期间行为抑郁的主要标志，以及杏仁核和终纹床核中的c-Fos表达。然而，LPS诱导的发热，血浆皮质酮升高，体重减轻和c-Fos在下丘脑和尾侧脑干的表达没有改变的IL-1 ra的i. c. v.输液。这些发现，连同我们先前的观察结果表明，i. c. v.输注IL-1 ra扩散到整个血管周围空间，其中巨噬细胞表达白细胞介素-1受体，可以解释为表明循环或局部产生的脑IL-1 β作用于这些细胞，在外周LPS给药后的APR期间引起行为抑制和边缘结构激活。
Although receptors for the pro-inflammatory cytokine interleukin-1 have long been known to be expressed in the brain, their role in fever and behavioural depression observed during the acute phase response (APR) to tissue infection remains unclear. This may in part be due to the fact that interleukin-1 in the brain is bioactive only several hours after peripheral administration of bacterial lipopolysaccharide (LPS). To study the role of cerebral interleukin-1 action in temperature and behavioural changes, and activation of brain structures during the APR, interleukin-1 receptor antagonist (IL-1ra; 100 mu g) was infused into the lateral brain ventricle 4 h after intraperitoneal (i.p.) LPS injection (250 mu g/kg) in rats. I.p. LPS administration induced interleukin-1 beta (IL-1 beta) production in systemic circulation as well as in brain circumventricular organs and the choroid plexus. Intracerebroventricular (i.c.v.) infusion of IL-1ra 4 h after i.p. LPS injection attenuated the reduction in social interaction, a cardinal sign of behavioural depression during sickness, and c-Fos expression in the amygdala and bed nucleus of the stria terminalis. However, LPS-induced fever, rises in plasma corticosterone, body weight loss and c-Fos expression in the hypothalamus and caudal brainstem were not altered by i.c.v. infusion of IL-1ra. These findings, together with our previous observations showing that i.c.v. infused IL-1ra diffuses throughout perivascular spaces, where macrophages express interleukin-1 receptors, can be interpreted to suggest that circulating or locally produced brain IL-1 beta acts on these cells to bring about behavioural depression and activation of limbic structures during the APR after peripheral LPS administration.