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Am J Physiol Regul Integr Comp Physiol 268: R1406-R1410, 1995;
0363-6119/95 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 268, Issue 6 1406-R1410, Copyright © 1995 by American Physiological Society

ARTICLES

Interferon-alpha acts at the preoptic hypothalamus to reduce natural killer cytotoxicity in rats

S. Take, D. Uchimura, Y. Kanemitsu, T. Katafuchi and T. Hori
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

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.


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