|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1992 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1991 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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.