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

我们最近证明，在大鼠体内注射干扰素α (ifna α)可导致脾脏自然杀伤（NK）细胞毒性的降低，这取决于中枢阿片受体和完整的脾神经支配。在本研究中，我们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。在脲- α氯醛麻醉大鼠中，ICV注射人重组干扰素α （1.5 × 10^3-10^4U/大鼠）可引起脾交感神经活动的剂量依赖性兴奋，而静脉给药纳洛酮可阻断这种兴奋。电刺激脾神经末梢（0.5mA,0.5msec,20Hz）可抑制脾脏NK细胞的细胞毒活性，可被纳多洛尔（β -拮抗剂）完全阻断，而普拉唑嗪（α -拮抗剂）则不能。结果表明，ifnalpha诱导的NK细胞活性抑制是通过β -肾上腺素能受体介导的脾交感神经激活过程引起的。此外，双侧刺激内侧视前下丘脑（MPO）抑制脾神经的活性，而损伤MPO或在MPO中微量注射ifn - α则增强其活性。这些发现提示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.