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Neuroendocrine Effects of Interferon-α in the Rat

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The Brain Immune Axis and Substance Abuse

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 373))

Abstract

We have previously found that recombinant human interferon-α2A (rHu-IFN- α2A) inhibits hypothalamo-pituitary-adrenocortical (HPA) axis activity following both peripheral and central administration. This effect is antagonized by µ-opioid receptor antagonists, suggesting transduction by this subtype of opioid receptors. We have now demonstrated that this effect is also observed with hybrid rHu-IFN-αA/D, rat kidney fibroblast-derived IFN-α, and recombinant rat IFN-α preparations. The inhibitory effects on HPA activity were observed after intraperitoneal (i.p.) injections of rHu-IFN- α2A (103 U), rHu-IFN- αA/D (104 U), and of Rat-IFN-α (1-10 U). Similar effects were observed with intracerebroventricular (i.c.v.) admini­stration of all four IFN-α preparations. No increases in plasma corticosterone concentrations were observed with doses of rHu-IFN-α A/D up to 106 U (i.p.) or 7X1 05 U (i.c.v.), but increases were found following i c v. administration of high doses of Rat-IFN-α (103 and 5X103 U). The inhibitory effects of all of the IFN-α preparations tested were antagonized by naloxone, but the stimulatory effects of 5X1 03 U Rat-IFN- α were not. Injections of rHu-IFN- α2A (104 U, i.p.) to urethane-anesthetized rats decreased the electrical activity of the majority of hypothalamic paraventricular nucleus (PVN) neurons tested, including putative corticotropin-releasing fac­tor- (CRF)-secreting neurons antidromically identified as projecting to the median eminence. Similarly, iontophoretic application of rHu-IFN-α2A decreased the electrical activity of such cells. These electrophysiological data suggest that the decreases in HPA activity evoked by IFN-α are mediated, at least in part, by a rapid inhibitory effect at the level of the corticotropin­releasing factor-secreting neurons.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics Department of Psychiatry, Louisiana State University Medical Center, 1501 Kings Highway, Shreveport, Louisiana, 71130, USA

    David Saphier

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  1. David Saphier
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Editors and Affiliations

  1. Hennepin County Medical Center and University of Minnesota, Minneapolis, Minnesota, USA

    Burt M. Sharp

  2. Temple University School of Medicine, Philadelphia, Pennsylvania, USA

    Toby K. Eisenstein

  3. Emory University School of Medicine, Atlanta, Georgia, USA

    John J. Madden

  4. University of South Florida College of Medicine, Tampa, Florida, USA

    Herman Friedman

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Saphier, D. (1995). Neuroendocrine Effects of Interferon-α in the Rat. In: Sharp, B.M., Eisenstein, T.K., Madden, J.J., Friedman, H. (eds) The Brain Immune Axis and Substance Abuse. Advances in Experimental Medicine and Biology, vol 373. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1951-5_29

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  • DOI: https://doi.org/10.1007/978-1-4615-1951-5_29

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5801-5

  • Online ISBN: 978-1-4615-1951-5

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