Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine production, and costimulatory molecules.

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spleen cells, macrophage-enriched adherent cells, or CD11b(+) purified macrophages, to spleen cells taken from withdrawn mice, restored immune responses.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.