ROLE OF PROLACTIN IN THE MODULATION OF NK AND LAK CELL-ACTIVITY AFTERSHORT-TERM OR LONG-TERM MORPHINE ADMINISTRATION IN NEOPLASTIC PATIENTS

In a previous work we demonstrated that chronic in vivo antalgic thera py of cancer patients with morphine reduced the endogenous cytotoxic a ctivity of natural killer (NK) cells, while increasing the development of lymphokine activated killer (LAK) cell cytotoxicity. In order to i nvestigate the mechanisms by which morphine affects NK and LAK cell fu nction further, we evaluated the modulation exerted by short- or long- term morphine administration on either NK/LAK cell cytotoxicities or p lasma levels of prolactin (PRL) and other immunomodulating neurohormon es. An intravenous morphine injection (10 mg) significantly increased the plasma levels of PRL, reduced the cytotoxic activity of NK cells, and increased the development of LAK cell activity 30 min after drug i njection in neoplastic patients. The administration of bromocriptine b efore the injection of morphine prevented both PRL. augmentation and t he increase in LAK cell activation, although it did not prevent the in hibition of NK cytotoxicity. The chronic oral administration of morphi ne (90+/-30 mg/day for 1 month) also resulted in higher PRL levels; th e NK and LAK cell activities were, respectively, lower than or higher than those found in neoplastic patients untreated with morphine. The p lasma levels of thyrotropin (TSH), adrenocorticotropic hormone (ACTH) and cortisol were not significantly modified in either short- or long- term experiments. The absolute number and the percentages of lymphocyt e populations, as well as the percentage of IL-2 receptors, were not m odified after short-term morphine administration whereas little change s of T lymphocyte populations and Mt cell number were observed after o ral treatment with morphine. In vitro morphine did not affect the deve lopment of LAK cell activity. In conclusion, our findings indicate tha t morphine reduces NK cytotoxicity and increases the development of LA K cell cytotoxicity after short- and long-term administration. The eff ect of morphine on LAK cell activation but not on Mt cell reduction is related to the modulation of PRL levels determined by the opioid drug . (C) 1997 International Society for Immunopharmacology.