HEPATIC AND SPLENIC PHAGOCYTOSIS IN FEMALE B6C3F1 MICE IMPLANTED WITHMORPHINE-SULFATE PELLETS

Morphine sulfate has previously been shown to produce a dose-dependent decrease in hepatic phagocytosis when administered as 8-, 25- and 75- mg pellets implanted subcutaneously. This study was undertaken to dete rmine the time course of suppression of hepatic and splenic phagocytos is after subcutaneous implantation of morphine sulfate pellets. Mice w ere implanted with either 75 mg of morphine sulfate or placebo pellets . The uptake of chromated sheep red blood cells by the liver and splee n was taken as an index of phagocytosis by resident Kuppfer cells or m acrophages, respectively. The results indicate that maximum suppressio n of hepatic phagocytosis by 67% occurred 18 hr after implantation of 75 mg of morphine sulfate. Hepatic phagocytic capacity returned to con trol levels within 48 hr of implantation. The initial time course of s uppression of splenic phagocytosis by 41% was similar to that of the l iver (maximum at 12 hr). However, splenic phagocytic capacity returned toward placebo levels over a longer period of time reaching control a fter 4 days after implantation. The opiate receptor antagonist, naltre xone (30-mg pellet), completely blocked the ability of morphine to sup press either hepatic or splenic phagocytosis. Corticosterone is known to increase in parallel with plasma morphine levels presumably through a hypothalamic-pituitary-adrenal axis. The glucocorticoid receptor an tagonist RU 486 was used to block the actions of corticosterone and in vestigate its possible role in morphine sulfate-induced suppression of phagocytosis. RU 486 (200 mg/kg) completely blocked morphine sulfate' s ability to suppress splenic phagocytosis. In contrast, RU 486 only p artially blocked morphine-induced suppression of hepatic phagocytosis. This initial study suggests that morphine sulfate suppresses hepatic phagocytosis primarily through an opiate receptor-mediated mechanism, whereas splenic phagocytosis is suppressed secondarily through a gluco corticoid receptor mechanism.