IMMUNOREGULATORY CYTOKINE PRODUCTION BY TUMOR-BEARING RAT SPLEEN-CELLS AND ITS MODULATION BY BLEOMYCIN

The chemotherapeutic agent bleomycin (BLM) increases cytokine production by mitogen-stimulated healthy rat spleen cells without altering the cellular composition of the spleen. In this study, the chronological production of interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF) by untreated and BLM-treated tumor-bearing rat spleen cells is examined. A significant decrease in the production of both IL-2 and TNF could be observed only 5 days after subcutaneous injection of syngeneic KMT-17 tumor cells. Decrease in cytokine production progressed with time with a slight recovery around day 10 after tumor challenge. Administration of BLM, 5 mg/kg, on day 8, restored IL-2 and IL-6 production and significantly increased TNF production by day 14 of tumor burden as compared with the amounts of cytokine produced by the mitogen-stimulated untreated tumor-bearing rat spleen cells. The response of the tumor-bearing rat spleen cells to concanavalin A (ConA), diminished when compared with that of normal rat spleen cells, could be restored to normal levels by treatment with BLM when examined at low concentrations of mitogen but was unaffected at higher concentrations of ConA. Histological examination of the tumor tissue, following continuous intraperitoneal treatment with BLM, 5 mg/kg, from day 8 to 12, shows disruption of cellular structure with significant infiltration of effector cells as compared with undisrupted organization with no visible infiltration of effector cells in the untreated rat tumors.