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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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
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