IL-23, a
cytokine, which is composed of the p40 subunit shared with
IL-12 and the IL-23-specific p19 subunit, has been shown to preferentially act on Th1 effector/memory CD4+ T cells and to induce their proliferation and IFN-gamma production. The
IL-23 is also reported to act on Th17-CD4+ T cells, which are involved in inducing tissue injury. In this study, we examined the antitumor effects associated with systemic administration of
IL-23 and their mechanisms in mouse
tumor system. Systemic administration of high-dose
IL-23 was achieved using in vivo electroporation of
IL-23 plasmid
DNA into the pretibial muscles of C57BL/6 mice. The
IL-23 treatment was associated with significant suppression of the growth of pre-existing MCA205
fibrosarcoma and prolongation of the survival of treated mice without significant toxicity when compared with those of the mice treated with EGFP. Although the therapeutic outcomes were similar to those with the
IL-12 treatment, the
IL-23 treatment induced characteristic immune responses distinctive to those of
IL-12 treatment. The
IL-23 administration even at the therapeutic levels did not induce detectable IFN-gamma concentration in the serum. In vivo depletion of CD4+ T cells, CD8+ T cells, or NK cells significantly inhibited the antitumor effects of
IL-23. Furthermore, the CD4+ T cells in the lymph nodes in the IL-23-treated mice showed significant IFN-gamma and
IL-17 response upon anti-CD3 mAb stimulation in vitro. These results and the ones in the IFN-gamma or
IL-12 gene knockout mice suggest that potent antitumor effects of
IL-23 treatment could be achieved when the Th1-type response is fully promoted in the presence of endogenously expressed
IL-12.