INTERLEUKIN-4-MEDIATED TUMOR SUPPRESSION IN NUDE-MICE INVOLVES INTERFERON-GAMMA

The molecular events during the anti-tumor response induced by interleukin (IL)-4 were investigated by quantitative polymerase chain reaction. The growth of Chinese hamster ovary cells transfected to produce IL-4 (CHO.T1) was strongly suppressed when cells were injected intraperitoneally into nude mice and this suppression was accompanied by the rapid accumulation of activated macrophages. Peritoneal cells from such mice were analyzed for mRNA induced by IL-4. Correlating with a high local IL-4 concentration, several transcripts were found to be up-regulated during the early phase of the anti-tumor response [IL-4 receptor, IL-5, tumor necrosis factor (TNF) and interferon (IFN)-gamma]. The functional relevance of the elevated mRNA levels was analyzed by injection of CHO.T1 cells together with anti-cytokine monoclonal antibodies (mAb). In contrast to anti-IL-5 and anti-TNF mAb, an anti-IFN-gamma mAb interfered with the anti-tumor response demonstrating the involvement of IFN-gamma during the IL-4-induced tumor suppression. Tumor growth in anti-IFN-gamma mAb-treated animals was significantly delayed in comparison to anti-IL-4 mAb-treated mice, suggesting that IFN-gamma-independent effector cells may also be involved.