CENTRAL INTERFERON-ALPHA INHIBITS NATURAL-KILLER CYTOTOXICITY THROUGHSYMPATHETIC INNERVATION

The brain has been known to produce high levels of interferon-alpha (I FN-alpha) during viral infections. We investigated the central and per ipheral mechanisms of the brain IFN-alpha-induced suppression of natur al killer (NK) cytotoxicity in the rat. The activity of NK cells in th e spleen and the peripheral blood decreased 30-120 min after intracere broventricular (icv) injection of recombinant human IFN-alpha of >1,00 0 U but not after its intraperitoneal injection. This effect was antag onized by pretreatment with icv naltrexone (NLTX). Splenic denervation was observed to completely abolish the IFN-alpha-induced suppression of NK activity, whereas bilateral adrenalectomy did not. Furthermore, this immunosuppression was blocked by an icv injection of an antagonis t of corticotropin-releasing factor (CRF), alpha-helical CRF-(9-41). T he icv injection of CRF resulted in reduced NK activity, which was not affected by NLTX. The results suggest that brain IFN-alpha activates the CRF system through central opioid receptors and thereby suppresses the NK cytotoxicity predominantly through splenic sympathetic innerva tion.