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Immune alterations in chronic morphine-treated rhesus monkeys
1Department of Microbiology, LSU Medical Center, New Orleans 70112-1393.
Abstract:
Both immune and neuroendocrine abnormalities have been documented in heroin abusers. We investigated immunocompetence of peripheral blood mononuclear cells (PBMs) among separate groups of rhesus monkeys that were drug naive or received morphine either infrequently (twice/week) or daily (3.2 mg/kg). Both infrequent and daily morphine-exposed monkeys showed a decrease (10%) in the percentage of CD4+ circulating lymphocytes and an increase (19%) in the percentage of CD8+ cells. However, monkeys exposed daily to morphine showed a 30% increase in the helper-inducer CD4+ lymphocytes, CD4+CD29+, compared to untreated controls. PBMs taken from animals exposed daily to morphine responded poorly to forskolin in the production of cAMP compared with cells obtained from untreated animals. However, cells from monkeys that received morphine infrequently had elevated levels of cAMP in response to forskolin. These results suggest relatively low doses of morphine have a significant effect on immunocompetence in rhesus monkeys which parallels the effects observed in the opioid-dependent human population. Therefore, rhesus monkeys will provide a beneficial animal model to study the effects of opioid compounds on immunocompetence during exposure, withdrawal and substitution drug therapy in opioid-dependent animals.
Insights
Morphine exposure alters immune cells in rhesus monkeys, affecting T-cell populations and cyclic AMP (cAMP) production. These findings in monkeys mirror human opioid abuse effects, suggesting a valuable model for studying opioid impacts on immunity.
Area of Science:
- Immunology
- Neuroendocrinology
- Pharmacology
Background:
- Opioid abuse is linked to immune and neuroendocrine system abnormalities.
- Understanding these effects is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the impact of morphine exposure on immunocompetence in rhesus monkeys.
- To establish a relevant animal model for studying opioid effects on the immune system.
Main Methods:
- Rhesus monkeys were divided into drug-naive, infrequent morphine, and daily morphine groups.
- Peripheral blood mononuclear cells (PBMs) were analyzed for lymphocyte percentages (CD4+, CD8+).
- Cellular response to forskolin, measuring cyclic AMP (cAMP) production, was assessed.
Main Results:
- Morphine exposure decreased CD4+ and increased CD8+ lymphocytes.
- Daily morphine increased helper-inducer CD4+ lymphocytes (CD4+CD29+).
- Daily morphine exposure impaired cAMP production in response to forskolin, while infrequent exposure elevated it.
Conclusions:
- Even low doses of morphine significantly affect rhesus monkey immunocompetence.
- These effects parallel those seen in opioid-dependent humans.
- Rhesus monkeys serve as a valuable model for studying opioid-related immune modulation.