Interleukin-2 (IL-2) induces corticotropin-releasing factor (CRF) release from the amygdala and involves a nitric oxide-mediated signaling; Comparison with the hypothalamic response

Jacob Raber, G. F. Koob, F. E. Bloom

Research output: Contribution to journalArticle

139 Scopus citations


Interleukin-2 (IL-2)-like immunoreactivity and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. IL-2 stimulates hypothalamic corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) release and that of pituitary adrenocorticotropin. The amygdala, known to contain high levels of CRF, is involved in stress-related reactions, including regulation of the hypothalamo-pituitary-adrenal axis. IL-2 will release AVP from both the hypothalamus and the amygdala, which further supports a role for cytokine effects in the amygdala in neuroimmune interactions. In the present study, we compared the effects of IL-2, acetylcholine and norepinephrine on the in vitro release of CRF from the amygdala or hypothalamus. In addition, we used these release systems to evaluate the possible involvement of nitric oxide (NO)-mediated signaling in CRF release. IL-2 stimulates CRF release in both regions, in a calcium- and dose-dependent manner. Nitroprusside, an NO generator, also induces CRF release. This IL-2- induced CRF release is antagonized by N9-methyl-L-arginine and hemoglobin, known NO antagonists. Finally, norepinephrine and acetylcholine induce CRF release. The norepinephrine-induced CRF release is antagonized by phentolamine and propranolol and the acetylcholine-induced release by atropine and mecamylamine, which suggests the involvement of both alpha and beta adrenergic receptors and both muscarinic and nicotinic receptors. The acetylcholine-induced CRF release is antagonized by N9-methyl-L-arginine, but the norepinephrine-induced response is not. These data support the suggestion that the amygdala may participate in communications between the neuroendocrine and immune systems.

Original languageEnglish (US)
Pages (from-to)815-824
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
Publication statusPublished - 1995
Externally publishedYes


ASJC Scopus subject areas

  • Pharmacology

Cite this