INTERFERON-ALPHA ACTS AT THE PREOPTIC HYPOTHALAMUS TO REDUCE NATURAL-KILLER CYTOTOXICITY IN RATS

We previously demonstrated that an intracerebroventricular injection o f recombinant human interferon-alpha (rhIFN-alpha) reduced the cytotox icity of splenic natural killer (NK) cells in rats and mice. In the pr esent study, we investigated the brain sites at which rhIFN-alpha acts to suppress splenic NK activity in unanesthetized rats implanted unil aterally with a chronic hypothalamic cannula. A microinjection of 200 U of rhIFN-alpha into the medial part of the preoptic hypothalamus red uced NK activity to similar to 60% of control 30 min after the injecti on. Administration of 50 U of rhIFN-alpha also decreased NK activity t o similar to 80%. The injection of 200 U of rhIFN-alpha into other hyp othalamic areas (lateral preoptic hypothalamus, ventromedial hypothala mus, lateral hypothalamus, and paraventricular nucleus) had no effect. The medial preoptic hypothalamus-rhIFN-alpha-induced immunosuppressio n was completely blocked by splenic denervation, but not by adrenalect omy. These results suggest that IFN-alpha suppresses splenic NK activi ty predominantly through the medial preoptic hypothalamus-sympathetic pathway.