HYPOTHALAMIC MODULATION OF SPLENIC NATURAL-KILLER-CELL ACTIVITY IN RATS

1. The cytotoxic activity of splenic natural killer cells measured by a standard chromium release assay in urethane and alpha-chloralose-ana esthetized rats was significantly suppressed 20 min after bilateral ab lation of the medial part of the preoptic hypothalamus (MPO). The supp ression was completely blocked by prior splenic denervation. The splen ic natural killer cell activity of MPO sham-lesioned rats or thalamus- lesioned rats, both having an intact splenic innervation, were not dif ferent from that of a non-treated control group. 2. Electrical stimula tion of the bilateral MPO (0.1 ms, 0.1-0.3 mA, 5-100 Hz) suppressed th e efferent activity of the splenic nerve in all six rats examined. The reduction of the nerve activity was accompanied by a transient fall i n blood pressure. An i.v. injection of phenylephrine (3 mug/0.3 ml) al so evoked a suppression of the nerve activity, which was accompanied b y transient hypertension, suggesting that the suppressive effect of th e MPO stimulation was independent of changes in blood pressure. On the other hand, a bilateral lesion of the MPO resulted in a sustained inc rease in the electrical activity of the splenic sympathetic nerve fila ments which lasted for more than 2 h. 3. Microinjection of monosodiuM- L-glutamate (0.1 and 0.01 M in 0.1 mul saline) unilaterally into the M PO evoked a transient suppression of the efferent discharge rate of th e splenic nerve activity within 1 min, which was also accompanied by a decrease in blood pressure. The injection of saline (0.1 mul) into th e MPO had no effect. The microinjection of recombinant human interfero n-alpha (200 and 2000 U in 0.1 mul saline) into the MPO dose dependent ly increased the splenic nerve activity without any change in blood pr essure. 4. In contrast, microinjection of interferon-alpha into the pa raventricular nucleus of the hypothalamus (PVN) had no effect on splen ic nerve activity, although an injection of glutamate increased the ne rve activity. 5. The present results, taken together with previous rep orts, suggest that the neuronal networks between the MPO and the splen ic sympathetic nerve, which may be activated by centrally administered interferon-alpha, are important in the suppression of the splenic cel lular immunity.