Abstract
Background: Our previous study showed that the combination of irinotecan (CPT-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. Materials and Methods: 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. Results: 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, which was not observed with LPS-activated splenocytes. 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. Conclusion: These results suggest that the interaction of SN-38 and OK-432 may support a type 1 T helper (Th1)-dominant state through increasing endogenous IL-12 production, mainly by macrophages.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2499-2504 |
| Number of pages | 6 |
| Journal | Anticancer Research |
| Volume | 23 |
| Issue number | 3 B |
| State | Published - May 1 2003 |
| Externally published | Yes |
Keywords
- CPT-11
- IL-12
- OK-432
- SN-38