Immune alterations in chronic morphine-treated rhesus monkeys.

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.