Early expression of interleukin-12, p40 subunit and IFN-gamma inhibits regression of AK-5 tumor.

Differential immune response of syngeneic animals to a rat histiocytoma AK-5 based on the route of transplantation was investigated. Spontaneous regression of subcutaneous tumor was observed in 55-60% of animals. On the other hand, when the tumor cells were injected intraperitoneally, none of the animals survived. Earlier studies from this laboratory indicated upregulation of Th-1-type cytokines, leading to early tumor regression when the tumor was transplanted subcutaneously. Hence we evaluated and compared the circulatory-cytokine profiles in both s.c. and i.p. tumor-injected animals. Our results show an early increase in the p40 subunit of IL-12, prolific increase in IFN-gamma and lower levels of IL-2 in i.p. tumor-injected animals. However, there were no significant differences in the levels of transcripts for these cytokines in either of the groups. Significantly, a lower level of cytotoxicity was observed with splenocytes from i.p. tumor-transplanted animals. Moreover, the cytotoxicity of IL-12-activated but not IL-2-activated NK cells was inhibited by sera (rich in IL-12, p40 subunit) from i.p. tumor-transplanted animals, suggesting the participation of p40 subunit in the regulation of tumor regression. Thus the present study suggests a possible translational regulation of Th-1-type cytokines in AK-5 tumor-host interaction.