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

我们最近证实，大鼠侧脑室注射干扰素α(IFNpha)可降低脾自然杀伤细胞(NK)的细胞毒作用，这依赖于中枢阿片受体和完整的脾神经支配。在本研究中，我们进一步研究了交感神经介导的免疫抑制的中枢和外周机制。在乌拉坦-α氯醛糖麻醉大鼠，侧脑室注射人重组人干扰素α(1.5×10~(-3)~10~(-4)U/只)产生剂量依赖性的脾交感神经兴奋，这种兴奋可被静脉注射纳洛酮所阻断。电刺激脾神经外周断端(0.5 mA，0.5 ms，20 Hz)可抑制脾NK细胞的杀伤活性，这种抑制作用可被β-受体拮抗剂纳多洛尔完全阻断，但不能被α-受体拮抗剂哌唑嗪所阻断。结果提示，干扰素α对NK细胞活性的抑制是通过β-肾上腺素能受体介导的脾交感神经激活过程实现的。此外，电刺激双侧视前内侧下丘脑(MPO)可抑制脾神经的活动，而损毁MPO或向MPO内微量注射肿瘤坏死因子α可增强其活性，提示MPO与脾交感神经之间的神经元网络可能在抑制脾细胞免疫中起重要作用。

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.