Interferon-alpha acts at the preoptic hypothalamus to reduce natural killer cytotoxicity in rats.
We previously demonstrated that an intracerebroventricular injection of recombinant human interferon-alpha (rhIFN-alpha) reduced the cytotoxicity of splenic natural killer (NK) cells in rats and mice. In the present study, we investigated the brain sites at which rhIFN-alpha acts to suppress splenic NK activity in unanesthetized rats implanted unilaterally with a chronic hypothalamic cannula. A microinjection of 200 U of rhIFN-alpha into the medial part of the preoptic hypothalamus reduced NK activity to approximately 60% of control 30 min after the injection. Administration of 50 U of rhIFN-alpha also decreased NK activity to approximately 80%. The injection of 200 U of rhIFN-alpha into other hypothalamic areas (lateral preoptic hypothalamus, ventromedial hypothalamus, lateral hypothalamus, and paraventricular nucleus) had no effect. The medial preoptic hypothalamus-rhIFN-alpha-induced immunosuppression was completely blocked by splenic denervation, but not by adrenalectomy. These results suggest that IFN-alpha suppresses splenic NK activity predominantly through the medial preoptic hypothalamus-sympathetic pathway.
Take
S
S
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Uchimura
D
D
Kanemitsu
Y
Y
Katafuchi
T
T
Hori
T
T
D000818:Animals; D001931:Brain Mapping; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007276:Injections, Intraventricular; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D008297:Male; D008845:Microinjections; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012016:Reference Values; D013154:Spleen / Q000276:immunology / Q000294:innervation; D013997:Time Factors
D007370:Interferon Type I; D011994:Recombinant Proteins