Effects of morphine tolerance and abstinence on cellular immune function.
Female B6C3F1 mice were rendered tolerant-dependent on morphine by a combination of injections and pellet implantation. Mice were injected with morphine sulfate (20 mg/kg, s.c.) twice a day on day 1. On day 2, they were implanted s.c. with a 75 mg morphine pellet for 3 days. On day 5, the pellets were either left intact (tolerant) or removed 8 h prior (abstinent) to carrying out the immune function tests. A high degree of tolerance to the analgesic and hypothermic effect of morphine developed as a result of this procedure. Similarly, physical dependence also developed as evidenced by the signs of the abrupt and naltrexone-precipitated abstinence syndrome. Implantation with morphine pellets resulted in a profound, statistically significant reduction in spleen and thymus weight and cellularities, with the greatest degree of reduction noted in abstinent animals. Morphine tolerance was associated with suppressed B-cell proliferation following in vitro stimulation, as well as interleukin-2 (IL-2) and interleukin-4 production by T-cells. NK cell activity was significantly reduced in morphine-tolerant, but not in morphine-abstinent, mice following a 24 h incubation in the presence or absence of IL-2. In comparison, the in vitro induction of cytotoxic T-cells was significantly depressed in morphine-abstinent, but not morphine-tolerant, animals. Exposure to morphine apparently had limited effect on macrophage function as assessed by production of tumor necrosis factor. These studies demonstrate a differential effect on immune effector and regulatory mechanisms in morphine tolerance and abstinence processes.
Department of Pharmacodynamics (M/C 865), University of Illinois at Chicago 60612.
H N
HN
Bhargava
P T
PT
Thomas
S
S
Thorat
R V
RV
House
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004361:Drug Tolerance; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000276:immunology*; D013375:Substance Withdrawal Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects
D016207:Cytokines; D009020:Morphine