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


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.


CONCLUSIONS
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.
Zhang
Bin
B
Division of Surgical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Fujimoto
Toshihiro
T
Kaneda
Atsuko
A
Mai
Masayoshi
M
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D019013:CD40 Antigens / Q000276:immunology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D000077146:Irinotecan; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010844:Picibanil / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic; D019013:CD40 Antigens; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D010844:Picibanil; D000077146:Irinotecan; D002166:Camptothecin