Role of central β-adrenergic receptors in regulating proinflammatory cytokine responses to a peripheral bacterial challenge
Role of central β-adrenergic receptors in regulating proinflammatory cytokine responses to a peripheral bacterial challenge
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DOI：
10.1016/j.bbi.2008.03.007
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发表时间：
2008-10-01
影响因子：
15.1
通讯作者：
Fleshner, Monika
中科院分区：
文献类型：
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作者：
Johnson, John D.;Cortez, Valerie;Fleshner, Monika
大脑中促炎细胞因子的升高对改变生理、行为和认知过程具有强大的影响。由于微生物/细胞因子不能穿过血脑屏障（BBB），因此在外周免疫挑战期间诱导脑细胞因子的机制仍不清楚。最近的研究表明，中枢 P-肾上腺素受体 (β-ADR) 可能介导脑白介素 1 β (IL-1) 的产生。这对外周免疫反应期间脑细胞因子的产生有直接影响，因为外周病原体和细胞因子通过外周神经和心室周围通路快速刺激脑干儿茶酚胺神经元。本研究探讨了外周大肠杆菌 (E. coli) 攻击后中枢 β-ADR 在调节脑细胞因子产生中的作用。向大鼠集中施用普萘洛尔（β-ADR拮抗剂）或媒介物，然后施用外周大肠杆菌或盐水，并在6小时后处死以测量细胞因子。普萘洛尔预处理完全阻断了大肠杆菌对脑ILA的诱导。令人惊讶的是，中心普萘洛尔还减弱了大肠杆菌诱导的外周细胞因子。为了检查中枢普萘洛尔给药后外周细胞因子反应减弱是否是由于普萘洛尔渗漏到大循环和外周β-阻断剂的阻断所致，纳多洛尔（不穿过BBB的β-ADR拮抗剂）在大肠杆菌之前外周给药。纳多洛尔给药不会阻断大肠杆菌后中枢细胞因子的产生，而是增强外周和中枢促炎细胞因子的产生。此外，异丙肾上腺素（β-ADR 激动剂）的中枢给药会导致脑内 IL-1 的产生呈时间依赖性增加。这些数据表明，中枢 β-ADR 可能在诱导大脑 IL-1 方面发挥关键作用，而外周 β-ADR 则抑制细胞因子对细菌攻击的反应。 (C) 2008 Elsevier Inc. 保留所有权利。
Elevation of proinflammatory cytokines in the brain have potent effects on altering physiological, behavioral, and cognitive processes. The mechanism(s) by which brain cytokines are induced during a peripheral immune challenge remains unclear since microorganisms/cytokines do not cross the blood-brain barrier (BBB). Recent studies indicate that central P-adrenergic receptors (beta-ADRs) may mediate brain interleukin-1 beta (IL-1) production. This has direct implications for the production of brain cytokines during a peripheral immune response since peripheral pathogens and cytokines rapidly stimulate brain-stem catecholamine neurons via peripheral nerves and circumventricular pathways. Studies here examine the role of central beta-ADRs in regulating brain cytokine production following peripheral Escherichia coli (E. coli) challenge. Rats were centrally administered propranolol (beta-ADR antagonist) or vehicle followed by peripheral E. coli or saline and sacrificed 6 h later for measurement of cytokines. Pre-treatment with propranolol completely blocked the induction of brain ILA following E. coli. Surprisingly, central propranolol also attenuated E. coli-induced peripheral cytokines. To examine whether the attenuated peripheral cytokine response following central propranolol administration was due leakage of propranolol into the general circulation and blockade of peripheral p-blockade, nadolol (beta-ADR antagonist that does not cross the BBB) was administered peripherally prior to E. coli. Nadolol administration did not block central cytokine production following E. coli, but instead enhanced both peripheral and central proinflammatory cytokine production. Furthermore, central administration of isoproterenol (beta-ADR agonist) results in a time-dependent increase in brain IL-1 production. These data demonstrate central beta-ADRs may play a critical role to induce brain IL-1, while peripheral beta-ADRs inhibit cytokine response to bacterial challenge. (C) 2008 Elsevier Inc. All rights reserved.