Endocrinology, Vol 135, 1346-1352, Copyright © 1994 by Endocrine Society

ARTICLES

Intracerebroventricular interleukin-1 alpha increases immunocyte beta- endorphin concentrations in the rat: involvement of corticotropin- releasing hormone, catecholamines, and serotonin

P Sacerdote, M Bianchi, B Manfredi and AE Panerai
Department of Pharmacology, University of Milan School of Medicine, Italy.

The opioid peptide beta-endorphin (BE) is synthesized and secreted by the cells of the immune system and has been shown to participate in the modulation of immune responses, e.g. during stress. Interleukin-1 (IL- 1) is a potent activator of the corticotropin-releasing hormone (CRH) system in the hypothalamus, and it has been shown to be involved in many stress responses, including immunosuppression. We studied the effect of centrally injected IL-1 alpha on immunocyte BE concentrations in the rat. IL-1 alpha (1 ng/rat, intracerebroventricularly) significantly (P < 0.01) increased the concentrations of the peptide in splenocytes, lymph node cells, and peripheral blood mononuclear cells 2 and 24 h after treatment. Intracerebroventricular, but not iv, administration of 2 micrograms IL-1 receptor antagonist blocked the IL- 1 alpha-induced increase. These effects were also prevented by the intracerebroventricular administration of the CRH receptor antagonist alpha-helical CRH-(9-41). Treatment with 6-hydroxydopamine and 5,7- dihydroxytryptamine, which deplete the catecholaminergic or the serotoninergic systems, respectively, blocked the increase in BE induced by the cytokine. In contrast, hypophysectomy and treatment with indomethacin did not modify the effect of IL. The increase in immunocyte BE, therefore, seems to depend on the activation of CRH, catecholamines, and serotonin, but to be independent of activation of the hypothalamus-pituitary-adrenal-axis and prostaglandins. The immunocyte BE increase could be involved in the immunosuppression induced by central IL-1 alpha.

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