Immunosuppression induced by central action of morphine is not blocked by mifepristone (RU 486).
Morphine causes immunosuppression by binding to opioid receptors on immune cells, or indirectly by acting on receptors in the brain. However, morphine exact mechanism of action has not been elucidated. In the present study, we investigated the role of glucocorticoids in morphine-mediated immunosuppression after acute action in the rat mesencephalon periaqueductal gray (PAG). Natural killer (NK) cell activity and T cell proliferation were used to evaluate potential indirect mechanisms of morphine action. Microinjection of morphine in the ventral-caudal aspect of the PAG significantly (p < 0.01) suppressed splenic NK cell cytotoxic activity (32% reduction), and antiTCR-, IL-2-, antiTCR + IL-2, and Con A-induced thymic (30% to 50% reduction) and splenic (35% to 70% reduction) lymphocyte proliferation compared with PAG-injected saline control animals. The glucocorticoid receptor antagonist mifepristone (RU 486) did not block the immunosuppressive effects of morphine, suggesting that such effects are independent of activation of the hypothalamic-pituitary-adrenal axis.
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D005938:Glucocorticoids; D006727:Hormone Antagonists; D007166:Immunosuppressive Agents; D015735:Mifepristone; D009020:Morphine