[Anti-tumor effect of IL-2 and hemin on murine renal cell carcinoma].
Hemin, which is the mitogenic oxidizing agent, has immunostinulatory properties for murine splenocytes. We studied the anti-tumor effect of hemin with IL-2 by using murine renal cell carcinoma (Renca). Treatment of cells with hemin and IL-2 resulted in a marked enhancement of mitogenicity and generation of cytotoxicity in vitro. These enhancements were achieved at low dose of IL-2. Splenocytes isolated from mice that had been treated with hemin and IL-2 incorporated increased amounts of 3H-thymidine during 20 hours incubation in vitro. Treatment with the combination of hemin and IL-2 was more effective than either hemin or IL-2 alone. The combination of hemin and IL-2 was effective in inducing cytotoxicity for Renca. Induction of cytotoxicity was optimal at the hemin concentration of 10 microM, and higher concentrations were less effective. In vivo administration of hemin and IL-2 in Renca bearing mice resulted in a significant survival prolongation. IL-2 alone, at the dose used, was ineffective. The anti-tumor effect was enhanced by administration of N-acetylcysteine and by nephrectomy. Since hemin can safely be administered to patients, it may represent a new class of biologic response modifiers that could enhance IL-2 mediated anti-tumor effects.
Tsuji
A
A
Department of Urology, National Defense Medical College, Saitama, Japan.
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D006427:Hemin / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D006427:Hemin