Neuroimmunomodulatory Actions of Hypothalamic Interferon-α
Neuroimmunomodulatory Actions of Hypothalamic Interferon-α
复制标题
下丘脑干扰素-α 的神经免疫调节作用
作者：
T. Hori;T. Katafuchi;Sachiko Take;N. Shimizu
最近的研究表明，大脑产生干扰素-α（IFN-α），以响应非炎症以及炎症应激，它可能在正常生理中发挥作用。当脑内给药时，IFN-α引起多种效应，包括发热、厌食、镇痛和中枢神经元活动的变化。这些反应被阿片受体拮抗剂纳洛酮抑制。这与表明重组人（rh）IFN-α与啮齿动物脑细胞膜中阿片受体结合的报告一致。结果表明，rhIFN-α以阿片受体依赖的方式改变了下丘脑腹内侧视前区（MPO）的温度敏感神经元和葡萄糖反应神经元的活动。由于已知产生阿片依赖性镇痛的应激可抑制脾自然杀伤细胞的细胞毒性，我们研究了β-内啡肽和rhIFN-α的给药是否可诱导类似的免疫抑制。我们发现，中央，但不是外周，这两种化合物注射抑制自然杀伤细胞（NK）的细胞毒性。进一步的研究表明，rhIFN-α通过阿片受体降低MPO神经元的活性，而MPO神经元活性的改变反过来又导致促肾上腺皮质激素释放因子神经元的激活，从而主要通过激活脾交感神经和β受体来抑制NK细胞的细胞毒性。脾细胞的受体机制。因此，IFN-α可以改变大脑活动，对免疫系统产生反馈作用。进一步的全细胞钳位分析表明，rhIFN-α抑制N-甲基-D-天冬氨酸诱导的MPO神经元膜电流反应不仅通过阿片受体介导，还可能通过神经元-胶质细胞相互作用产生活性氧中间产物一氧化氮和前列腺素类化合物。
Recent studies have revealed that the brain produces interferon-α (IFN-α) in response to noninflammatory as well as inflammatory stress and that it might have a role in normal physiology. When administered intracerebrally, IFN-α causes diverse effects including fever, anorexia, analgesia and changes in the central neuronal activities. These responses are inhibited by the opioid receptor antagonist naloxone. This is consistent with the reports suggesting that recombinant human (rh) IFN-α binds to opioid receptors in rodent brain membrane. We revealed that rhIFN-α altered the activity of thermosensitive neurons in the medial preoptic area (MPO) and glucose-responsive neurons in the ventromedial hypothalamus in an opioid-receptor-dependent way. As a stress which produces opioid-dependent analgesia is known to suppress the cytotoxicity of splenic natural killer cells, we investigated whether the administration of β-endorphin and rhIFN-α may induce a similar immunosuppression. We found that central, but not peripheral, injection of both compounds inhibited natural killer (NK) cytotoxicity. Further studies revealed that rhIFN-α decreased the activity of MPO neurons via opioid receptors and the altered activity of MPO neurons in turn resulted in the activation of corticotropin-releasing factor neurons, thereby suppressing NK cytotoxicity predominantly through activation of the splenic sympathetic nerve and β-receptor mechanisms in splenocytes. Thus, IFN-α may alter the brain activity to exert a feedback effect on the immune system. Further detailed whole-cell clamping analyses on neuronal mechanisms in rat brain tissue slices showed that the inhibitory effect of rhIFN-α on N-methyl-D-aspartate-induced membrane current responses of MPO neurons was mediated not only by opioid receptors but also by the local production of reactive oxygen intermediates, nitric oxide and prostanoids, possibly due to neuron-glial cell interaction.
影响因子：
3.3
作者：
X. Chen;C. Gillis
通讯作者：
X. Chen;C. Gillis
DOI：
10.1073/pnas.86.16.6348
发表时间：
1989-08-01
影响因子：
11.1
作者：
LIEBERMAN, AP;PITHA, PM;SHIN, ML
通讯作者：
SHIN, ML
人α干扰素受体：神经节苷脂参与其中吗？
DOI：
10.1089/jir.1984.4.305
发表时间：
1984
期刊：
Journal of interferon research
影响因子：
--
作者：
Gupta,SL;Raziuddin,A;Sarkar,FH
通讯作者：
Sarkar,FH