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 histiocytom a AK-5 based on the route of transplantation was investigated. Spontan eous regression of subcutaneous tumor was observed in 55-60% of animal s. On the other hand, when the tumor cells were injected intraperitone ally, none of the animals survived. Earlier studies from this laborato ry indicated upregulation of Th-l-type cytokines, leading to early tum or 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 i n the p40 subunit of IL-12, prolific increase in IFN-gamma and lower l evels of IL-2 in i.p. tumor-injected animals. However, there were no s ignificant differences in the levels of transcripts for these cytokine s in either of the groups. Significantly, a lower level of cytotoxicit y was observed with splenocytes from i.p. tumor-transplanted animals. Moreover, the cytotoxicity of IL-12-activated but not IL-2-activated N K cells was inhibited by sera (rich in IL-12, p40 subunit) from i.p. t umor-transplanted animals, suggesting the participation of p40 subunit in the regulation of tumor regression. Thus the present study suggest s a possible translational regulation of Th-1-type cytokines in AK-5 t umor-host interaction.