Suppression of splenic macrophage functions following acute morphine action in the rat mesencephalon periaqueductal gray.
Morphine action in the periaqueductal gray (PAG) matter of the mesencephalon suppresses T cell proliferation and NK cell activity through actions at mu opioid receptors. We investigated the effect of acute microinjection of morphine in the rat PAG on macrophage function. We found that morphine injection in the PAG significantly (p <.01) suppressed nitric oxide production by untreated (82 +/- 23% suppression), IFN-gamma-primed (57 +/- 11% suppression), and LPS-activated (50 +/- 7% suppression) splenic macrophages and did not alter macrophage viability. In contrast, IFN-gamma- and LPS-activated macrophages from PAG-injected saline rats generated an increased output of nitric oxide, which was associated with significant (p <.01) reduction in cell viability. Morphine significantly (p <.01) inhibited TNF-alpha production by LPS-activated macrophages (28 +/- 8% inhibition compared with PAG-injected saline rats). In addition, morphine significantly (p <. 05) inhibited phagocytosis of Candida albicans by resident macrophages (40 +/- 20% inhibition compared with that of macrophages from PAG-injected saline rats). Responses of resident or activated macrophages from PAG-injected saline and untreated control groups did not differ significantly. The results of this ex vivo study suggest that suppressive effects of morphine on macrophage functions may contribute to increased susceptibility to infectious diseases and cancer associated with drug abuse.
Gomez-Flores
R
R
Department of Biomedical and Therapeutic Sciences, University of Illinois, Peoria, Illinois 61656, USA.
Suo
J L
JL
Weber
R J
RJ
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D009573:Nitrites / Q000032:analysis; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000701:Analgesics, Opioid; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D009020:Morphine; D007371:Interferon-gamma