Effect of tumor cells on the activation of murine lymphocytes and macrophages by cisplatin and FK565

Abstract

Murine peritoneal macrophages on in vitro treatment with cisplatin (55 μg/ml or FK565 (10 μg/ml) showed an enhanced production of tumor necrosis factor (TNF) and reactive nitrogen intermediates (RNI). Similarly, treatment of splenic lymphocytes with these agents also led to an enhanced production of TNF. Co-incubation of macrophages or splenic lymphocytes with P815 (a murine mastocytoma) cells in vitro in the absence of cisplatin or FK565 also resulted in an augmented TNF production, however, it had no effect on the RNI production by macrophages. TNF production of cisplatin-or FK565-treated macrophages got synergistically enhanced in the presence of P815 cells whereas the production of RNI was inhibited. Incubation of splenic lymphocytes with P815 cells in the presence of cisplatin or FK565 resulted in an inhibition of TNF production. Indomethacin-treated P815 cells were observed to be less effective in inhibiting nitrite production of macrophages compared to untreated tumor cells. Pretreatment of P815 cells with cisplatin or FK565 before co-incubation did not alter the TNF production of macrophages whereas it inhibited the same in lymphocytes. This study shows that activation of macrophages and lymphocytes is independently influenced by P815 tumor cells in combination with chemoimmunotherapeutic drugs cisplatin and FK565.