Irinotecan enhances IL-12 production by OK-432-activated murine macrophages

6004 Our previous study showed that the combination of Irinotecan(CTP-11)and OK-432 had an additive antitumor effect.The purpose of this study was to analyze the mechanism by which this combined treatment had an effect on immunity. To investigate the immune effects of murine splenocytes stimulated by SN-38(the active form of CPT-11) and OK-432, endogenous interleukin(IL)-12 p70 production was assayed by ELISA and flow cytometry. Endogenous IL-12 production was increased by SN-38 stimulation of cultures of OK-432-activated splenocytes from C57BL/6, C3H and Balb/c mice, IL-12 production by splenocytes was higher at an early stage after tumor inoculation. SN-38 and OK-432 stimulated IL-12 production in cultures of peritoneal exudate macrophages(PEM), and T cell cooperation was essential in cultured splenocytes. These results suggest that the interaction of SN-38 and OK-432 may support a type 1 T helper-dominant state through increaseing endogenous IL-12 production, mainly by macrophages.