Priming effect of morphine on the production of tumor necrosis factor-α by microglia: Implications in respiratory burst activity and human immunodeficiency virus-1 expression

C. C. Chao, G. Gekker, W. S. Sheng, S. Hu, M. Tsang, P. K. Peterson

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94 Scopus citations

Abstract

Opiates alter a variety of functional activities of the somatic immune system; within the central nervous system, however, their effects on immune responses are unknown. In the present study, we investigated the effect of morphine on the release of tumor necrosis factor (TNF)-α from murine neonatal microglia. Microglial cell cultures did not release TNF-α when incubated with morphine alone; however, an enhanced (P < .01) release of TNF- α was observed when cultures were first primed with morphine for 24 h and then stimulated with lipopolysaccharide. A bell-shaped dose-response curve was observed for the priming effect of morphine; maximal enhancement of TNF- α release (310 ± 15% of control) was detected at a concentration of 10- 10 M morphine. Pretreatment of microglia for 30 min with opioid receptor antagonists (i.e. naloxone and β-funaltrexamine) completely blocked the priming effect of morphine. In addition, morphine treatment amplified (P < .01) the priming effect of lipopolysaccharide on phorbol myristate acetate- triggered superoxide anion production by microglial cell cultures, and this effect was abrogated (P < .01) by anti-TNF-α antibody. Furthermore, culture supernatants derived from microglial cell cultures that had been treated with morphine before stimulation with lipopolysaccharide had an increased capacity to upregulate human immunodeficiency virus-1 expression in the latently infected promonocytic clone U1. This effect was also blocked by anti-TNF-α antibody. These findings suggest that morphine primes microglia for enhanced production of TNF-α which could alter several functional activities of these cells within the brain.

Original languageEnglish (US)
Pages (from-to)198-203
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume269
Issue number1
StatePublished - 1994

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