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Immunoregulatory cytokine release in rat spleen cell cultures after treatment with bleomycin and its analogues in vivo

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Summary

We have studied the immunological effects that accompany a change in the chemical structure of a group of antineoplastic antibiotics by comparing the immunoregulatory cytokine release during mitogen-stimulated spleen cell culture after in vivo drug treatment. Whereas bleomycin and peplomycin increased cytokine levels in culture supernatants when compared with supernatants from untreated control rat spleen cell cultures, liblomycin generally reduced cytokine levels under the same culture conditions. We then compared these results with the antitumor effects of equivalent doses of the three drugs against a highly antigenic rat fibrosarcoma, KMT-17, both in vivo and in vitro. The results suggest that the immunoaugmenting effects of these antitumor antibiotics are essential for an optimal antitumor effect in vivo, and that these effects can be drastically altered by modification of the chemical structure of the drugs employed.

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References

  1. Abdul Hamied TA, Parker D, Turk JL (1986) Potentiation of the release of interleukin-2 by bleomycin. Immunopharmacology 12: 127

    Google Scholar 

  2. Abdul Hamied TA, Turk JL (1987) Enhancement of interleukin-2 release in rats by treatment with bleomycin and Adriamycin in vivo. Cancer Immunol Immunother 25: 245

    Google Scholar 

  3. Ahmed K, Turk JL (1989) Effect of anticancer agents neothramycin, aclacinomycin, FK-565 and FK-156 on the release of interleukin-2 and interleukin-1 in vitro. Cancer Immunol Immunother 28: 87

    Google Scholar 

  4. Armstrong JA (1971) Semi-micro, dye-binding assay for rabbit interferon. Applied Microbiol 21: 723

    Google Scholar 

  5. Cohen S, Salazar D, Wicher J (1983) Adriamycin-induced activation of NK activity may initially involve LAF production. Cancer Immunol Immunother 15: 188

    Google Scholar 

  6. Ehrke JM, Maccubin D, Ryoyama K, Cohen SA, Mihich E (1986) Correlation between Adriamycin-induced augmentation of interleukin-2 production and of cell-mediated cytotoxicity in mice. Cancer Res 46: 54

    Google Scholar 

  7. Gillis S, Ferm MM, Ou W, Smith KA (1978) T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol 120: 2027

    Google Scholar 

  8. Hancock EJ, Kilburn DG (1982) The effects of cyclophosphamide on in vitro cytotoxic responses to syngeneic tumor. Cancer Immunol Immunother 14: 51

    Google Scholar 

  9. Hasan SI, Ahmed K, Turk JL (1990) Effect of anticancer drugs on the release of tumor necrosis factor in vitro. Cancer Immunol Immunother 30: 363

    Google Scholar 

  10. Hersh E (1974) Immunosuppressive agents. In: Sartoli AC, Johs DG (eds) Antineoplastic and immunosuppressive agents, vol 1. Springer, Berlin Heidelberg New York, p 577

    Google Scholar 

  11. Hosokawa M, Morikawa K, Kobayashi H (1983) Enhancement of antitumor activity of peritoneal macrophages by an antitumor antibiotic; bleomycin in tumor-bearing rats. In: Aoki T, Tsubura E, Urushizaki I (eds) Manipulation of host defence mechanisms. Exerpta Medica, Tokyo, p 2

    Google Scholar 

  12. Hosokawa M, Xu Z-Y, Morikawa K, Hamada J, Kobayashi H (1988) Host immune responses to tumor cells augmented by bleomycin and their therapeutic effects on rat fibrosarcoma. Mol Biother 1: 74

    Google Scholar 

  13. Komatsu T, Koide T, Ishihara K (1989) Antitumor effect of NK313 and PEP on human malignant melanoma (SK-14) in nude mice (in Japanese). Proc Jp Cancer Assoc Abstr 386

  14. Kuramochi H, Motegi A, Takahashi K, Takeuchi T (1988) DNA cleavage activity of liblomycin (NK313), a novel analog of bleomycin. J Antibiot (Tokyo) 41: 1846

    Google Scholar 

  15. Lazo JS, Braun ID, Labaree DC, Schisselbaur JC, Meandzija B, Newman R, Kennedy KA (1989) Characteristics of bleomycin-resistant phenotypes of human cell sublines and circumvention of bleomycin resistance by liblomycin. Cancer Res 49: 185

    Google Scholar 

  16. Lindsten T, June CH, Ledbetter JA, Stella G, Thompson CB (1989) Regulation of lymphokine mRNA stability by a surface-mediated T cell activation pathway. Science 244: 339

    Google Scholar 

  17. Matsuura A, Ishii Y, Yuasa H, Narita H, Kon S, Takami T, Kikuchi K (1984) Rat T lymphocyte antigens comparable with mouse Lyt-1 and Lyt-2,3 antigenic systems: characterisation by monoclonal antibodies. J Immunol 132: 316

    Google Scholar 

  18. Matthews N, Neale ML (1987) Cytotoxicity assays for tumour necrosis factor and lymphotoxin. Lymphokines and interferons. IRL Press, Oxford, p 221

    Google Scholar 

  19. Mihich E (1975) Immunosuppression in cancer therapeutics. Transpl Proc 7: 275

    Google Scholar 

  20. Morikawa K, Hosokawa M, Hamada J, Sugawara M, Kobayashi H (1985) Host-mediated therapeutic effects produced by appropriately timed administration of bleomycin on a rat fibrosarcoma. Cancer Res 45: 1502

    Google Scholar 

  21. Morikawa K, Hosokawa M, Hamada J, Xu Z-Y, Kobayashi H (1986) Possible participation of tumoricidal macrophages in the therapeutic effect of bleomycin on a transplantable rat fibrosarcoma. Cancer Res 46: 684

    Google Scholar 

  22. Morikawa K, Okada F, Hosokawa M, Kobayashi H (1987) Enhancement of therapeutic effects of recombinant interleukin 2 on a transplantable rat fibrosarcoma by the use of a sustained release vehicle, pluronic gel. Cancer Res 47: 37

    Google Scholar 

  23. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55

    Google Scholar 

  24. Parker D, Turk JL (1984) Potentiation of T-lymphocyte function of bleomycin. Immunopharmacology 7: 109

    Google Scholar 

  25. Riesbeck K, Anderson J, Gullberg M, Forsgren A (1989) Fluorinated 4-quinolones induce hyperproduction of interleukin 2. Proc Natl Acad Sci USA 86: 2809

    Google Scholar 

  26. Schwartz HS, Grindey GB (1973) Adriamycin and daunorubicin: a comparison of antitumor activities and tissue uptake in mice following immunosuppression. Cancer Res 33: 1837

    Google Scholar 

  27. Takahashi K, Ekimoto H, Minamide S, Nishikawa K, Kuramochi H, Motegi A, Nakatani T, Takita T, Takeuchi T, Umezawa H (1987) Liblomycin, a new analogue of bleomycin. Cancer Treat Rev 14: 169

    Google Scholar 

  28. Takita T, Ogino T (1987) Peplomycin and liblomycin, new analogues of bleomycin. Biomed Pharmacother 41: 219

    Google Scholar 

  29. Tueni EA, Newman RA, Baker FL, Ajani JA, Fan D, Spitzer G (1989) In vitro activity of bleomycin, tallysomycin S10b, and liblomycin against fresh human tumor cells. Cancer Res 49: 1099

    Google Scholar 

  30. Umezawa H, Suhora Y, Takita T, Maeda K (1966) Purification of Bleomycins. J Antibiot [A] 19: 210

    Google Scholar 

  31. Umezawa H, Maeda K, Takeuchi T, Toshioka O (1966) New antibiotics bleomycin A and B. J Antibiot [A] 19: 200

    Google Scholar 

  32. Xu Z-Y, Hosokawa M, Morikawa K, Kobayashi H (1986) Enhanced susceptibility of target KMT-17 cells to activated macrophages by treatment with the antitumor agent bleomycin. Cancer Immunol Immunother 23: 46

    Google Scholar 

  33. Xu Z-Y, Hosokawa M, Morikawa K, Hatakeyama K, Kobayashi H (1988) Overcoming suppression of antitumor immune reactivity in tumor-bearing rats by treatment with bleomycin. Cancer Res 48: 6658

    Google Scholar 

  34. Yamashina K, Oikawa T, Kasai M, Naiki M, Chiba I, Kobayashi H (1986) Development of highly immunogenic variants of a rat fibrosarcoma line during in vitro cultivation. Cancer Immunol Immunother 21: 45

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Kita-15, Nishi-7, Kita-Ku, 060, Sapporo, Japan

    Mark Micallef, Masuo Hosokawa, Toshiyuki Shibata, Zhi-bo Yang & Hiroshi Kobayashi

  2. Department of Microbiology, Hokkaido University School of Medicine, Kita-15, Nishi-7, Kita-Ku, 060, Sapporo, Japan

    Akio Nakane & Tomonori Minagawa

Authors
  1. Mark Micallef
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  2. Masuo Hosokawa
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  3. Toshiyuki Shibata
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  4. Akio Nakane
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  5. Zhi-bo Yang
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  6. Tomonori Minagawa
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  7. Hiroshi Kobayashi
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Micallef, M., Hosokawa, M., Shibata, T. et al. Immunoregulatory cytokine release in rat spleen cell cultures after treatment with bleomycin and its analogues in vivo. Cancer Immunol Immunother 33, 33–38 (1991). https://doi.org/10.1007/BF01742525

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  • DOI: https://doi.org/10.1007/BF01742525

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