ENHANCEMENT OF TUMOR-GROWTH BY MORPHINE AND ITS POSSIBLE MECHANISM INMICE

The effect of morphine on tumor growth of EL-4 leukemia in C57BL/6 mic e and of Sarcoma 180 carcinoma in ddY mice was studied. Local subcutan eous tumor growth was enhanced by morphine (10 mg/kg, s.c.) given dail y for 10 d. This effect was inhibited by preadministration of the opio id antagonist naloxone. However, naloxone alone had no significant eff ect on tumor growth. Morphine also enhanced tumor growth in C57BL/6 mi ce inoculated i.p. with P388 as well as Meth-A cell in Balb/c mice. Ho wever, incubation of morphine with cultures of EL-4, P388, MM-46 and M eth-A cells failed to enhance tumor growth. Mice given morphine displa yed marked atrophy and reduced cellularity of the spleen and thymus. T he humoral response to sheep erythrocytes and T- and B-cell responses to foreign antigens were suppressed, and the lymphocyte proliferative response to T- and B-cell mitogens (concanavalin A and bacterial lipop olysaccharide, respectively) was attenuated. Morphine exerted an inhib itory effect on the immune response which was antagonized by the conco mitant administration of naloxone. These data suggest that the enhance ment of tumor growth by the administration of morphine is the result o f a overall immunosuppresive effect. The significance of the immunomod ulatory effect of morphine is discussed in this report.