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

Bin Zhang, Toshihiro Fujimoto, Atsuko Kaneda, Masayoshi Mai

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)2499-2504
Number of pages6
JournalAnticancer Research
Volume23
Issue number3 B
StatePublished - May 1 2003
Externally publishedYes

Keywords

  • CPT-11
  • IL-12
  • OK-432
  • SN-38

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