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Updated: Aug 30, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine production, and costimulatory
Rahil T Rahim1, Joseph J Meissler, Lily Zhang
1Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
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spleen cells, macrophage-enriched adherent cells, or CD11b(+) purified macrophages, to spleen cells taken from withdrawn mice, restored immune responses.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.
Insights
Morphine withdrawal significantly impairs immune cell function, specifically the plaque-forming cell (PFC) response. This study reveals that restoring macrophage function can reverse this immunosuppression, highlighting a key mechanism of opioid withdrawal effects on immunity.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Opioid withdrawal, including abrupt (AW) and precipitated (PW) withdrawal, is known to suppress immune responses.
- Previous research demonstrated over 80% suppression of the in vitro plaque-forming cell (PFC) response to sheep red blood cells 24 hours post-withdrawal.
Purpose of the Study:
- To investigate the underlying mechanisms of morphine withdrawal-induced immunosuppression.
- To identify the specific immune cell populations and molecular factors involved in the suppressed immune response during morphine withdrawal.
Main Methods:
- Spleen cells from mice undergoing morphine withdrawal were analyzed.
- Immune responses were assessed by adding normal unfractionated spleen cells, macrophage-enriched adherent cells, or purified CD11b(+) macrophages to cultures from withdrawn mice.
- Splenic mRNA and protein levels of key cytokines (IL-1beta, IL-1Ra, TNF-alpha, IL-12, IFN-gamma) were measured.
- The effect of adding IL-1beta or IFN-gamma to cultures from abruptly withdrawn mice was evaluated.
Main Results:
- Restoration of immune responses was observed upon the addition of normal spleen cells, macrophage-enriched cells, or purified macrophages to spleen cells from withdrawn mice.
- Decreased splenic mRNA and/or protein levels of IL-1beta, IL-1Ra, TNF-alpha, IL-12, and IFN-gamma were detected in spleen cells from mice undergoing withdrawal.
- The addition of IL-1beta or IFN-gamma to cultures from abruptly withdrawn mice reversed the observed immunosuppression.
Conclusions:
- Morphine withdrawal leads to a significant deficit in macrophage function.
- Impaired macrophage function is a key contributor to the immunosuppression observed during morphine withdrawal.
- Cytokine deficits, particularly involving IL-1beta and IFN-gamma, play a role in the suppressed immune response.
