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.
Wu
H K
HK
Third Department of Internal Medicine, University of Tokyo.
Hirai
H
H
Inamori
K
K
Kitamura
K
K
Takaku
F
F
D000818:Animals; D002455:Cell Division; D005260:Female; D007111:Immunity, Cellular; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology
D015848:Interleukin-5; D015847:Interleukin-4