IL-2 induces vasopressin release from the hypothalamus and the amygdala: role of nitric oxide-mediated signaling.
The neuropeptide arginine vasopressin (AVP) can replace the cytokine interleukin 2 (IL-2) as a T-cell mitogen for the induction of interferon gamma (IFN gamma) expression in splenic cultures. IL-2-like and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. Regulatory functions for IL-2 in the CNS have been suggested. In addition to the spleen, AVP might also mediate some IL-2 effects centrally. In the present study, we evaluated the effect of IL-2 on the in vitro release of AVP from the hypothalamus and amygdala. In addition, we used these release systems to study the possible involvement of NO-mediated signaling in AVP release, based on the reported detection of nitric oxide synthase (NOS) in the hypothalamus and amygdala. IL-2 rapidly stimulates AVP release in both regions, in a calcium- and dose-dependent manner. In addition, nitroprusside also induces AVP release. Norepinephrine also induces AVP release from both the hypothalamus, as well as the amygdala. The norepinephrine-induced AVP release is antagonized by phentolamine, but not by propranolol, suggesting an alpha-adrenergic receptor-mediated AVP response in both brain regions. The IL-2- and acetylcholine-induced AVP release is antagonized by Ng-methyl-L-arginine, indicating a role for NO in this AVP release. Ng-methyl-L-arginine does not affect the norepinephrine-induced AVP release. A stimulatory effect of IL-2 on hypothalamic CRF release and plasma ACTH has already been reported. Our results suggest that in addition to CRF, AVP may also mediate the IL-2 stimulation of ACTH secretion. These data further suggest that in addition to the hypothalamus, the amygdala may also play a role in the bidirectional communication between neuroendocrine and immune systems. Understanding the mode of interaction between IL-2 with AVP could clarify the pathophysiologic or toxic effects of high brain levels of IL-2.
Raber
J
J
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Bloom
F E
FE
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000032:analysis; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016587:Antimutagenic Agents; D007376:Interleukin-2; D001127:Arginine Vasopressin; D009599:Nitroprusside; D009569:Nitric Oxide; D003035:Cobalt; D011433:Propranolol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; C018021:cobaltous chloride; D000109:Acetylcholine; D009638:Norepinephrine; D010646:Phentolamine