Rapid Elevation of Plasma Interleukin-6 by Morphine Is Dependent on Autonomic Stimulation of Adrenal Gland

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 300; no. 1; pp. 213 - 219
• Main Authors: Houghtling, Richard A, Bayer, Barbara M
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.01.2002
• Subjects: Adrenal Glands - drug effects; Adrenal Glands - physiology; Adrenal Medulla - physiology; Adrenalectomy; Animals; Autonomic Nervous System - physiology; Chlorisondamine - pharmacology; Corticosterone - blood; Dose-Response Relationship, Drug; Ganglionic Blockers - pharmacology; Injections, Intraventricular; Interleukin-6 - blood; Male; Morphine - pharmacology; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Narcotics - pharmacology; Rats; Rats, Sprague-Dawley; Stimulation, Chemical
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.300.1.213

Several studies have demonstrated that opioids regulate a number of immune cell functions either through direct mechanisms or through the modulation of central nervous system outputs. It has been previously shown that morphine increases serum interleukin-6 (IL-6) levels; however, the mechanism by which this effect is produced is unknown. In the present study, experiments were designed to address the potential role of central opioid receptors, peripheral autonomic ganglia, and activation of the adrenals in the elevation of plasma IL-6 after morphine administration. A rapid and significant (2-fold) increase in plasma IL-6 was observed after morphine administration (10 mg/kg s.c.) to rats. This effect of morphine peaked within 30 min and remained elevated for at least 2 h. Central microinjection of morphine (10 μg/2 μl i.c.v.) mimicked the effects of peripherally administered morphine and was completely blocked by naltrexone (10 mg/kg s.c.) pretreatment. Pretreatment with a ganglionic blocker, chlorisondamine (0.5 mg/kg i.p.), also blocked the elevation of IL-6 by morphine, suggesting a role of the autonomic nervous system. In adrenalectomized animals, morphine administration did not increase IL-6 levels, whereas in adrenal demedullated animals, the effect of morphine remained intact. Thus, the adrenal cortex may be a potential source of IL-6, because IL-6 mRNA has been localized in the adrenal gland. Collectively, these data suggest a unique mechanism by which stimulation of central opioid receptors results in the elevation of plasma IL-6 through autonomic activation specifically of the adrenal cortex.