Roles of hypothalamo-sympathetic nervous system and circumventricular organs in stress-immune interactions.

我们最近已经证明，在大鼠ICV注射干扰素α（IFN α）导致脾自然杀伤细胞（NK）的细胞毒性，这取决于中央阿片受体和完整的脾神经支配减少。本研究进一步探讨了交感神经介导的免疫抑制的中枢和外周机制，在麻醉大鼠侧脑室注射人重组IFN α（1.5 × 10^3 -10^4U/只），可引起剂量依赖性的脾交感神经兴奋，而静脉注射纳洛酮可阻断这种兴奋。电刺激脾神经末梢（0.5mA，0.5msec，20 Hz）可抑制脾内NK细胞的杀伤活性，并能被β受体拮抗剂纳多洛尔完全阻断，而不能被α受体拮抗剂哌唑嗪阻断。结果表明，IFN α诱导的NK细胞活性抑制是通过β-肾上腺素能受体介导的过程激活脾交感神经引起的。此外，双侧刺激下丘脑内侧视前区（MPO）可抑制脾神经的活动，而损毁MPO或向MPO内微量注射IFN α则可增强脾神经的活动，提示MPO与脾交感神经之间的神经网络可能在脾细胞免疫抑制中起重要作用。

We have recently demonstrated that ICV injection of interferon alpha (IFNalpha) in rats resulted in a reduction of splenic natural killer (NK) cytotoxicity, which depends on central opioid receptors and intact splenic innervation. In the present study, we further examined the central and peripheral mechanisms of the immunosuppression mediated by the sympathetic nerves.In urethane-alpha chloralose anesthetized rats, ICV injection of human reconbinat IFNalpha (1.5x10^3-10^4U/rat) produced a dose-dependent excitation of splenic sympathetic nerve activity, which was blocked by intravenous administration of naloxone. Electrical stimulation of the peripheral cut ends of splenic nerves (0.5mA,0.5msec,20Hz) resulted in the suppression of the cytotoxic activity of NK cells in the spleen, which was completely blocked by nadolol (beta-antagonist), but not by prazosin (alpha-antagonist). The results suggest that IFNalpha-induced suppression of NK cell activity is brought about by the activation of splenic sympathetic nerves through a beta-adrenergic receptor mediated process. Furthermore, bilateral stimulation of the medial preoptic hypothalamus (MPO) suppressed the activity of splenic nerves, while lesioning the MPO or microinjection of IFNalpha into the MPO enhanced it.These findings suggest that the neuronal network between the MPO and the splenic sympathetic nerves may play an important role in the suppression of splenic cellular immunity.