Role of human blood monocytes in up-regulation of lymphokine (interleukin-2)-activated killer cell activity with cisplatin and FK-565.

The role of cisplatin (CP) and FK-565 in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by interleukin-2 (IL-2) was examined. Treatment of peripheral-blood mononuclear cells (PBMC) with CP or FK-565 in the presence of IL-2 resulted in a significant increase in LAK activity against NK-resistant Raji cells, as assessed by the 4-hour 51Cr release assay, depending on the dose of CP, FK-565 and IL-2. Up-regulation of IL-2-induced LAK activity by CP/FK-565 was significantly higher in whole PBMC as compared to PBMC depleted of monocytes. Addition of different numbers of monocytes to cultures of lymphocytes plus IL-2 along with CP or FK-565 resulted in a significant up-regulation of LAK activity depending on the number of monocytes added. Pretreatment of monocytes for 2 h with CP or FK-565 before addition of lymphocytes plus IL-2 resulted in significant up-regulation of LAK activity as compared to untreated monocytes. Culture supernatant of CP- or FK-565-treated monocytes also significantly up-regulated IL-2-induced LAK activity of lymphocytes. The results of the present investigation suggest that up-regulation of LAK activity by CP and FK-565 in human PBMC is monocyte-mediated. Further, our data demonstrate that tumor necrosis factor and IL-1 play an important role in the up-regulation of LAK activity by monocytes that have been pretreated with FK-565 or CP. These results indicate that CP and FK-565 may be useful in modulating the immune response during treatment of neoplasia with IL-2 and LAK therapies.