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Suppression of human peripheral blood mononuclear cell function by methadone and morphine
P K Peterson1, G Gekker, C Brummitt
1Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota 55415.
Abstract:
Recent studies have shown that in vitro exposure of peripheral blood mononuclear cells (PBMC) to morphine results in suppressed respiratory-burst activity of monocytes and impaired interferon-gamma (IFN-gamma) production by lymphocytes. To investigate the potential in vivo effect of an opiate on these cell functions, PBMC were obtained from patients maintained on methadone. These freshly isolated mononuclear cells had a significantly impaired capacity to generate superoxide anion (O2-) in response to phorbol myristate acetate (PMA), while production of IFN-gamma by concanavalin A-stimulated cells was intact. After cell culture for 48 h, the defective O2- generating capacity was sustained. Also, culturing PBMC from healthy controls in the presence of methadone or morphine at concentrations as low as 10(-12) M caused significant suppression of PMA-stimulated O2- release. Because reactive oxygen intermediates produced by PBMC may participate in host defense against opportunistic pathogens in AIDS, these results underscore the need for investigations of the biological consequences of opiate-mediated immunosuppression.
Insights
Opioid medications like methadone and morphine can suppress immune cell function. This study found that these drugs impair the ability of peripheral blood mononuclear cells (PBMC) to produce critical defense molecules.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- In vitro studies show morphine impairs monocyte respiratory burst and lymphocyte interferon-gamma (IFN-gamma) production.
- Investigating in vivo opiate effects on immune cell function is crucial.
Purpose of the Study:
- To assess the in vivo impact of methadone on peripheral blood mononuclear cell (PBMC) functions.
- To determine if methadone or morphine can suppress immune cell activity in healthy individuals.
Main Methods:
- PBMC were isolated from patients on methadone maintenance therapy.
- Superoxide anion (O2-) production and IFN-gamma release were measured in response to stimulants like phorbol myristate acetate (PMA) and concanavalin A.
- PBMC from healthy controls were cultured with methadone or morphine.
Main Results:
- PBMC from methadone patients showed impaired O2- generation capacity, which persisted after 48h culture.
- IFN-gamma production by lymphocytes remained intact in methadone patients.
- In vitro exposure of healthy control PBMC to low concentrations of methadone or morphine suppressed PMA-stimulated O2- release.
Conclusions:
- In vivo methadone exposure impairs PBMC superoxide anion generation.
- Opiates like methadone and morphine can directly suppress immune cell function at low concentrations.
- Further research is needed on the clinical implications of opiate-induced immunosuppression, particularly concerning host defense against opportunistic infections.