Interleukin‐4‐mediated tumor suppression in nude mice involves interferon‐γ

Abstract

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.

Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression.

“…However, treatment of mice with neutralizing antibodies against VCAM-1 or IL-5 does not completely block eosinophil infiltration into tumor cells (20,27). In contrast, IFN-,y production is increased in this process and treatment of mice with antibodies that neutralize IFN-,y does prevent tumor killing (28). The cellular source of eotaxin mRNA found after IL-4 tumor cell transplantation is not known, but we have seen that treatment of endothelial cells with IFN-y induces expression of eotaxin mRNA.…”

IL-4 synergistically enhances both IL-2– and IL-12–induced IFN-γ expression in murine NK cells

“…Studies in IL-4-deficient mice suggest that IL-4 is required for the generation of tumor-specific Th1 cells. 74 Constitutive IL-4 expression from transgenic tumor lines has been linked to IFN-␥ function in delaying tumor growth 75 as well as in tumor rejection. 76 The mechanism(s) that explains the role of IL-4 in enhancing some cell-mediated functions is not clear.…”

Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity

“…IL-4 can effectively induce DC to produce the major Th1-inducing cytokine-bioactive IL-12, and the expression of Gene Therapy IL-4 by tumor cells transfected to secrete IL-4, or in a transgenic mouse model, led to induction of IFN-␥ in vivo and tumor suppression. 46 IL-4 injection around the tumor-draining lymph node, where T cell priming probably occurs, lead to an antitumor response, showing that not only the time point, but also the amount of IL-4 required for induction of tumor immunity are crucial. 47 In this study, we found significant IL-4 production within the tumors of AdMDC-treated mice.…”