Anti‐tumor Effects of Interleukin‐4 and Interleukin‐5 against Mouse B Cell Lymphoma and Possible Mechanisms of Their Action

We investigated the anti‐tumor effects of recombinant mouse interleukin (IL)‐4 and IL‐5 by using a transplantable B cell lymphoma 38C13 cell line as a model. Daily local administration of either IL‐4 or IL‐5 produced moderate but significant inhibition of the rate of local tumor growth and prolongation of mean survival time (MST) in syngeneic C3H/HeJ mice; these anti‐tumor effects appeared to plateau at low doses. Histopathologic and immuno‐histochemical examination revealed necrotic changes in the cytokine‐treated tumors, associated with infiltration of inflammatory cells such as eosinophils, macrophages, and lymphocytes. The infiltrating lymphocytes were found to be Thy‐1.2(+) T cells. To elucidate the importance of T cells, the rate of tumor growth and the MSTs were compared between athymic T cell‐deficient BALB/c nude mice and immunocompetent C3H/HeJ mice. In the nude mice the transplanted tumor grew more rapidly and the MST was shorter than in the normal mice, suggesting a significant contribution of infiltrating T cells in the anti‐tumor effects of the interleukins. Lastly, in vitro, growth inhibition of the 38C13 cells was observed in a dose‐dependent manner at relatively high concentrations of either cytokine. Therefore, we conclude that both IL‐4 and IL‐5 have moderate anti‐tumor effects against 38C13 B cell lymphoma both in vivo and in vitro, and that the observed in vivo anti‐tumor effects are probably mediated both by tumoristatic action of infiltrating cells, such as eosinophils, macrophages and T lymphocytes, and by direct anti‐proliferative action of the recombinant cytokines.