Central interferon-alpha inhibits natural killer cytotoxicity through sympathetic innervation.
The brain has been known to produce high levels of interferon-alpha (IFN-alpha) during viral infections. We investigated the central and peripheral mechanisms of the brain IFN-alpha-induced suppression of natural killer (NK) cytotoxicity in the rat. The activity of NK cells in the spleen and the peripheral blood decreased 30-120 min after intracerebroventricular (icv) injection of recombinant human IFN-alpha of > 1,000 U but not after its intraperitoneal injection. This effect was antagonized 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 antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF-(9-41). The 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 innervation.
Take
S
S
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Mori
T
T
Katafuchi
T
T
Hori
T
T
D000315:Adrenalectomy; D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003714:Denervation; D007276:Injections, Intraventricular; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology*
D016898:Interferon-alpha; D011994:Recombinant Proteins; D009271:Naltrexone; D003346:Corticotropin-Releasing Hormone