Document 0070
 DOCN  M9460070
 TI    Priming effect of morphine on the production of tumor necrosis
       factor-alpha by microglia: implications in respiratory burst activity
       and human immunodeficiency virus-1 expression.
 DT    9408
 AU    Chao CC; Gekker G; Sheng WS; Hu S; Tsang M; Peterson PK;
       Neuroimmunobiology and Host Defense Laboratory, Minneapolis; Medical
       Research Foundation, Minnesota.
 SO    J Pharmacol Exp Ther. 1994 Apr;269(1):198-203. Unique Identifier :
       AIDSLINE MED/94223535
 AB    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)-alpha
       from murine neonatal microglia. Microglial cell cultures did not release
       TNF-alpha when incubated with morphine alone; however, an enhanced (P <
       .01) release of TNF-alpha 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-alpha 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 beta-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-alpha
       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-alpha
       antibody. These findings suggest that morphine primes microglia for
       enhanced production of TNF-alpha which could alter several functional
       activities of these cells within the brain.
 DE    Acquired Immunodeficiency Syndrome/MICROBIOLOGY/PHYSIOPATHOLOGY  Animal
       Cells, Cultured  HIV-1/*PHYSIOLOGY  Lipopolysaccharides/PHARMACOLOGY
       Mice  Mice, Inbred BALB C  Microglia/*DRUG
       EFFECTS/*METABOLISM/MICROBIOLOGY  Morphine/*PHARMACOLOGY  Respiratory
       Burst/*DRUG EFFECTS  Stimulation, Chemical  Superoxides/METABOLISM
       Support, U.S. Gov't, P.H.S.  Tumor Necrosis Factor/*BIOSYNTHESIS
       Up-Regulation (Physiology)/DRUG EFFECTS/PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).