1. Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine production, and costimulatory molecules.
- Author
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Rahim RT, Meissler JJ, Zhang L, Adler MW, Rogers TJ, and Eisenstein TK
- Subjects
- Animals, Antigen Presentation drug effects, Antigen Presentation immunology, Antigens, CD biosynthesis, Apoptosis drug effects, Apoptosis immunology, B7-2 Antigen, Cells, Cultured, Coculture Techniques, Cytokines biosynthesis, Cytokines genetics, Female, Hemolytic Plaque Technique, Leukocyte Count, Macrophage Activation drug effects, Macrophage Activation immunology, Macrophages drug effects, Macrophages metabolism, Membrane Glycoproteins biosynthesis, Mice, Mice, Inbred C3H, RNA, Messenger antagonists & inhibitors, RNA, Messenger biosynthesis, Spleen cytology, Spleen drug effects, Spleen metabolism, Substance Withdrawal Syndrome metabolism, Time Factors, B7-1 Antigen metabolism, Cytokines antagonists & inhibitors, Immunosuppressive Agents adverse effects, Macrophages immunology, Membrane Glycoproteins antagonists & inhibitors, Morphine adverse effects, Spleen immunology, Substance Withdrawal Syndrome immunology
- Abstract
We have previously shown that abstinence from morphine by either abrupt (AW) or precipitated (PW) withdrawal induces greater than 80% suppression in the capacity to mount an in vitro plaque-forming cell (PFC) response to sheep red blood cells at 24-h post withdrawal. Present studies on the mechanisms of immunosuppression showed that addition of normal unfractionated spleen cells, macrophage-enriched adherent cells, or CD11b(+) purified macrophages, to spleen cells taken from withdrawn mice, restored immune responses. Spleen cells from mice undergoing withdrawal also had decreased splenic mRNA and/or protein levels of IL-1beta, IL-1Ra, TNF-alpha, IL-12, and IFN-gamma. Addition of IL-1beta or IFN-gamma to AW cultures was able to reverse their immunosuppression. These results strongly suggest that morphine withdrawal results in a deficit of macrophage function.
- Published
- 2003
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