concanavalin-a and Substance-Withdrawal-Syndrome

We have previously shown that abrupt withdrawal (AW) from morphine induces greater than 80% immunosuppression in murine spleen cells, as assessed by the capacity to mount an in vitro plaque-forming cell response to sheep red blood cells. Present studies about the mechanisms of immunosuppression following AW showed that addition of highly enriched (CD11b+) splenic macrophages (obtained by cell sorting or magnetic separation) from AW mice to cultures of normal, unfractionated spleen cells suppressed immune responses. Further, addition of highly enriched (CD19+) B cells (but not T cells) from AW mice to normal cells was also immunosuppressive. B cells from AW mice were also able to inhibit the proliferative response of normal spleen cells to concanavalin A but not to lipopolysaccharide. Overall, the data suggest that immunosuppression by AW spleen cells is a result of active suppression by macrophages and B cells.

Topics: Acute Disease; Animals; Antigens, CD19; B-Lymphocytes; CD11 Antigens; Cell Proliferation; Cells, Cultured; Coculture Techniques; Concanavalin A; Disease Models, Animal; Female; Immune Tolerance; Immunomagnetic Separation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C3H; Morphine; Morphine Dependence; Narcotics; Spleen; Substance Withdrawal Syndrome

Young and middle-aged CBA mice were injected with "street" heroin in increasing doses for 14 days. Volume density of perisinusoid argirophilic fibers increased in both age groups (the increase being more pronounced in middle-aged mice), while the levels of spontaneous, LPS- and ConA-stimulated splenocyte proliferation decreased in young mice. Six months after heroin discontinuation further progress of liver fibrosis was observed in young mice.

Topics: Age Factors; Animals; Cells, Cultured; Concanavalin A; Fibrosis; Heroin; Lipopolysaccharides; Liver; Mice; Mice, Inbred CBA; Spleen; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

The immunosuppression accompanying illicit drug use has been shown to contribute to a decreased resistance to a variety of pathogens; however, there is relatively little information on how long these effects persist following withdrawal from chronic drug exposure. To begin to address this question, Sprague-Dawley male rats were administered either cocaine (10 mg/kg, i.p., b.i.d.) for 7 days or morphine (escalating doses up to 40 mg/kg, s.c., b.i.d.) for a 10-day period. Control groups of animals received similar saline injections for equivalent time periods. Drug administration was abruptly discontinued and animals were sacrificed at 2, 24, 72 or 96 h following the last dose. At these time points, proliferation responses of peripheral blood T-lymphocytes stimulated by concanavalin A (Con A) and plasma levels of corticosterone were measured. Plasma corticosterone levels of cocaine- or morphine-treated animals were found to be significantly elevated 24 h following drug cessation as compared to saline animals. At this time, proliferation responses were significantly decreased and were further suppressed during cocaine and morphine withdrawal at 96 and 72 h, respectively. These results suggest that abrupt cessation of cocaine or morphine administration leads to activation of stress-related pathways that may contribute to an increased susceptibility of infection during the initial withdrawal phase.

Topics: Analysis of Variance; Animals; Cocaine; Concanavalin A; Corticosterone; Lymphocytes; Male; Mitogens; Morphine; Narcotics; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome; Thymidine; Time Factors; Tritium