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

The chemotherapeutic agent bleomycin (BLM) increases cytokine producti on 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 examin ed. A significant decrease in the production of both IL-2 and TNF coul d be observed only 5 days after subcutaneous injection of syngeneic KM T-17 tumor cells. Decrease in cytokine production progressed with time with a slight recovery around day 10 after tumor challenge. Administr ation 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 c ompared with the amounts of cytokine produced by the mitogen-stimulate d untreated tumor-bearing rat spleen cells. The response of the tumor- bearing rat spleen cells to concanavalin A (ConA), diminished when com pared with that of normal rat spleen cells, could be restored to norma l levels by treatment with BLM when examined at low concentrations of mitogen but was unaffected at higher concentrations of ConA. Histologi cal examination of the tumor tissue, following continuous intraperiton eal 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 o f effector cells in the untreated rat tumors.