Effect of morphine on lipopolysaccharide-induced tumor necrosis factor-alpha production in vivo: involvement of the sympathetic nervous system.
Morphine treatment modulates a variety of immunological parameters, including tumor necrosis factor-alpha (TNF-alpha) production by activated macrophages in vitro. The aim of our study was to clarify the effect of morphine on lipopolysaccharide (LPS)-induced TNF-alpha production in vivo. Plasma TNF-alpha levels of mice were determined by ELISA. Subcutaneous injection of morphine decreased LPS-induced TNF-alpha production throughout the response, an effect that was dose-dependent and reversible by naloxone. Blockade of the sympathetic transmission by chlorisondamine prevented the inhibitory effect of morphine on TNF-alpha production. It is concluded that (i) systemic administration of morphine inhibits LPS-induced TNF-alpha production in vivo via 'classic' opioid receptors; (ii) this effect requires intact sympathetic outflow. Since the increased incidence of bacterial and viral infections in opioid addicts is well documented, it is suggested that the inhibitory effect of morphine on TNF-alpha production might play a substantial role in the increased vulnerability of these individuals to certain infections.
Bencsics
A
A
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Elenkov
I J
IJ
Vizi
E S
ES
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D009020:Morphine