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Interleukin-1α: Its possible roles in cancer therapy

  • Published:
Biotherapy

Abstract

Our studies on recombinant human IL-1α polypeptide were summarized with respect to molecular cloning, production, quantitative assay systems, antitumor activity, myelorestorative activity and augmentation of host resistance to infections.

Recombinant human IL-1α (18 kDa) was produced through the expression of the cloned human IL-1α cDNA inEscherichia coli and purified to an endotoxin-free homogeneous polypeptide. The human IL-1α inhibited dose-dependently the growth of syngeneic murine tumors transplanted in mice and completely regressed the tumors in some cases, and its antitumor activity was significantly enhanced in combination with indomethacin. The human IL-1α accelerated the recovery of the numbers of peripheral leukocytes and neutrophils in a dose-dependent manner at a dose as low as 10 ng/mouse/day in myelo suppressed mouse model produced by administering anticancer chemotherapeutic drugs. The myelorestorative effect of IL-1α was observed not only on leukocytes/neutrophils, but also on platelets in myelosuppressed mice. In addition, the human IL-1α markedly augmented dose-dependently resistance of normal and leukopenic mice to various microbial infections.

These results suggested that recombinant human IL-1α might be useful for cancer therapy from the viewpoints of improving adverse effects such as myelosuppression caused by chemotherapy and/or radiation therapy and preventing infections. In addition, use of IL-1α may permit more intensive chemo- and radiation therapies using higher doses. Finally, the antitumor activity of the IL-1α itself may play an important role.

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Abbreviations

ADM:

adriamycin

BRM:

biological response modifier

CAT:

chloramphenicol acetyltransferase

CDDP:

cis-platin

CFU-C:

colony forming unit in culture

CSF:

colony stimulating factor

CHX:

cycloheximide

CPA:

cyclophosphamide

5-FLU:

5-fluorouracil

IND:

indomethacin

IL-1:

interleukin-1

i.m.:

intramuscular

i.p.:

intraperitoneal

i.t.:

intratu moral

i.v.:

intravenous

LAF:

lymphocyte-activating factor

MMC:

mitomycin C

McAB:

mono clonal antibody

MDP:

muramyl dipeptide

PMA:

phorbol-12-myristate-13-acetate

s.c.:

subcutaneous

TNF:

tumor necrosis factor

References

  1. Dinarello CA. Interleukin-1: amino acid sequences, multiple biological activities and comparison with tumor necrosis factor (cachectin). Year Immunol 1986; 2: 68–89.

    PubMed  Google Scholar 

  2. Auron PE, Webb AC. Molecular biology of interleukin 1. Lymphokines 1987; 4: 33–61.

    Google Scholar 

  3. Dinarello CA. Interleukin-1 and its biological related cytokines. Adv Immunol 1989; 44: 153–205.

    PubMed  Google Scholar 

  4. Auron PE, Webb AC, Rosenwasser LJ, Mucci SF, Rich A, Wolff SM, Dinarello CA. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Aci USA 1984; 81: 7907–11.

    Google Scholar 

  5. Lomedico PT, Gubler U, Hellmann CP, Dukovich M, Giri JG, Pan YE, Collier K, Seminow R, Chua AO, Mizel SB. Cloning and expression of murine intereukin-1 cDNA in Escherichia coli. Nature (London) 1984; 312: 458–62.

    Google Scholar 

  6. Yamada M, Furutani Y, Yamayoshi M, Notake M, Yamagishi J. Novel DNA encoding human interleukin 1 (in Japanese). Japanese Patent Application 278, 665/84, Dec. 25, 1984

  7. Furutani Y, Notake M, Yamayoshi M, Yamgishi J, Nomura H, Ohue M, Furuta R, Fukui T, Yamada M, Nakamura S. Cloning and characteriziation of the cDNAs for human and rabbit interleukin-1 precursor. Nucleic Acids Res 1985; 13: 5869–82.

    PubMed  Google Scholar 

  8. March CJ, Mosley B, Larsen A, Cerretti DP, Braedt G, Price V, Gillis S, Henney CS, Kronheim SR, Grabstein K, Conlon PJ, Hopp TP, Cosman D. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature (London) 1985; 315: 641–7.

    Google Scholar 

  9. Gray PW, Glaister D, Chen E, Goeddel DV, Pennica D. Two interleukin genes in the mouse: cloning and expression of the cDNA for murine interleukin lβ. J Immunol 1986; 137: 3644–8.

    PubMed  Google Scholar 

  10. Furutani Y, Nomura H, Notake M, Yamayoshi M, Ohue M, Yamagishi J, Furuta R, Fukui T, Yamada M, Nakamura S. Production of recombinant human interleukin-1 in Escherichia coli (in Japanese). Proc Jpn Soc Immunol 1985; 15: 380.

    Google Scholar 

  11. Yamada M, Yamayoshi M, Furuta R, Kotani H, Asaka Y, Nakata K, Yoshida H, Kashimoto S, Nakamura S. Biochemical and biological properties of recombinant human interleukin-1 alpha. Abst Sixth Int Congress Immunol 1986: 344.

  12. Nakamura S, Nakata K, Kashimoto S, Yoshida H, Yamada M. Antitumor effect of recombinant human interleukin 1 alpha against murine syngeneric tumors. Jpn J Cancer Res (Gann) 1986; 77: 767–73.

    Google Scholar 

  13. Nakata K, Kashimoto S, Yoshida H, Oku T, Nakamura S. Augmented antitumor effect of recombinant human Interleukin-1α by indomethacin. Cancer Res 1988; 48: 584–8.

    PubMed  Google Scholar 

  14. Sohmura Y, Matsui Y, Furuichi H, Matsuoka N. Myelorestorative effect of recombinant human interleukin-1 alpha in mice (in Japanese). Biotherapy (Tokyo) 1989; 3: 287–91.

    Google Scholar 

  15. Ozaki Y, Ohashi T, Minami A, Nakamura S. Enhanced resistance of mice to bacterial infection induced by recombinant human interleukin-la. Infect Immun 1987; 55: 1436–40.

    PubMed  Google Scholar 

  16. Minami A, Fujimoto K, Ozaki Y, Nakamura S. Augmentation of host resistance to microbial infections by recombinant human interleukin-1α. Infect Immun 1988; 56: 3116–20.

    PubMed  Google Scholar 

  17. Lehrach H, Diamond D, Wozny JM, Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry 1977; 16: 4743–51.

    PubMed  Google Scholar 

  18. Gray PW, Leung DW, Pennica D, Yelverton E, Najarian R, Simonsen CC, Derynck R, Sherwood PJ, Wallace DM, Berger SL, Levinson AD, Goeddel DV. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature (London) 1982; 295: 503–8.

    Google Scholar 

  19. Gurdon JB, Lane CD, Woodland HR, Marbaix G. Use of frog eggs and oocytes for the study of messenger RNA and its translation in living cells. Nature (London) 1971; 233: 177–82.

    Google Scholar 

  20. Gubler U, Hoffman BJ. A simple and very efficient for generating cDNA libraries. Gene 1983; 25: 263–9.

    PubMed  Google Scholar 

  21. Maniatis T, Fritsch EF, Sambrook J. eds. Molecular cloning: a laboratory manual. New York: Cold Spring Harbor Laboratory, 1982.

    Google Scholar 

  22. Furutani Y, Notake M, Fukui T, Ohue M, Nomura H, Yamada M, Nakamura S. Complete nucleotide sequence of the gene for human interleukin 1 alpha. Nucleic Acids Res 1986; 14: 3167–79.

    PubMed  Google Scholar 

  23. Carthew RW, Chodosh LA, Sharp PA. An RNA polymerase II transcription Factor binds to an upstream element in the adenovirus major late promoter. Cell 1985; 43: 439–48.

    PubMed  Google Scholar 

  24. Modi WS, Masuda A, Yamada M, Oppenheim JJ, Matsushima K, O'Brien SJ. Chromosomal localization of the human interleukin 1α(IL-1α) gene. Genomics 1988; 2: 310–4.

    PubMed  Google Scholar 

  25. Webb AC, Collins KL, Auron PE, Eddy RL, Nakai H, Byers MG, Haley LL, Henry WM, Shows TB. Interleukin-1 gene(ILI) assigned to long arm of human chromosome 2. Lymph Res 1986; 5: 77–85.

    Google Scholar 

  26. Nakano K, Okugawa K, Hayashi H, Abe S, Sohmura Y, Tsuboi T. Establishment of dye-uptake method (A375 assay) for quantitative measurement of IL-1: correlation with LAF assay. Develop biol Standard 1988; 69: 93–101.

    Google Scholar 

  27. Sunahara N, Kawata S, Furuta R, Yamayoshi M, Yamada M, Kurooka S. Preparation of monoclonal anti human interleukin 1α and its application to enzyme immunoassay (in Japanese). Proc Jpn Cancer Assoc 1986: 343.

  28. Sunahara N, Kawata S, Kaibe K, Furuta R, Yamayoshi M, Yamada M, Kurooka S. Differential determination of recombinant human interleukin-1α and its deamidated derivative by two sandwich enzyme immunoassays using monoclonal antibodies, comparison with a polyclonal antibody-based competitive enzyme immunoassay. J Immunol Methods 1989; 119: 75–82.

    PubMed  Google Scholar 

  29. Dinarello CA. Studies on the biological properties of purified and recombinant human interleukin-1. Meth Find Exp Clin Pharmacol 1986; 8: 57–61.

    Google Scholar 

  30. Onozaki K, Matsushima K, Aggarwal BB, Oppenheim JJ. Human interleukin 1 is a cyctocidal factor for several tumor cell lines. J Immunol 1985; 135: 3962–8.

    PubMed  Google Scholar 

  31. Onozaki K, Matsushima K, Kleinerman ES, Saito T, Oppenheim J. Role of interleukin 1 (IL1) in promoting human monocyt-mediated tumor cytotoxicity. J Immunol 1985; 135: 314–20.

    PubMed  Google Scholar 

  32. Dempsey RA, Dinarello CA, Mair JW, Rosenwasser LJ, Allegretta M, Brown TE, Darkinson DR. The differential effects of human leukocytic pyrogen/lymphocyte activating factor, T cell growth factor, and interferons on human natural killer activity. J Immunol 1982; 129: 2504–10

    PubMed  Google Scholar 

  33. Farrar WL, Mizel SB, Farrar JJ. Participation of lymphocyte activating factor (interleukin 1) in the induction of cytotoxic T cell responses. J Immunol 1980; 124: 1371–77.

    PubMed  Google Scholar 

  34. Yamashita U, Shirakawa F. Restoration of impaired T cell functions in tumor-bearing mice by the administration of interleukin 1. Jpn J Cancer Res (Gann) 1987; 78: 270–8.

    Google Scholar 

  35. Kasahara T, Mukaida N, Hatake K, Motoyoshi K, Kawai T, Shirai-Nakano, K. Interleukin 1 (IL-1)-dependent lymphokine production by human leukemic T cell line HSB.2 subclones. J Immunol 1985; 134: 1682–9.

    PubMed  Google Scholar 

  36. Hellerstein MK, Meydani SN, Meydani M, Wu K, Dinarello CA. Interleukin-I induced anorexia in the rats: influence of prostaglandins. J Clin Invest 1989 (in press).

  37. Neta R, Oppenheim JJ, Douches SD. Interdependence of the radioprotective effects of human recombinant interleukin 1α, tumor necrosis factor α, granulocyte colony-stimulating factor, and murine recombinant granulocyte macrophage colony-stimulating factor. J Immunol 1988; 140: 108–11.

    PubMed  Google Scholar 

  38. Ulich TR, Del Castillo J, Keys M, Granger GA, Ni RX. Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-α-induced changes in circulating numbers of neutrophils and lymphocytes. J Immunol 1987; 139: 3406–15.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Laboratories, Dainippon Pharmaceutical Co., Ltd., 33-94, Enoki, 564, Suita, Osaka, Japan

    Masaaki Yamada, Yasunobu Sohmura, Shinichi Nakamura & Masahisa Hashimoto

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  1. Masaaki Yamada
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  2. Yasunobu Sohmura
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  3. Shinichi Nakamura
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  4. Masahisa Hashimoto
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Yamada, M., Sohmura, Y., Nakamura, S. et al. Interleukin-1α: Its possible roles in cancer therapy. Biotherapy 1, 327–338 (1989). https://doi.org/10.1007/BF02171009

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  • DOI: https://doi.org/10.1007/BF02171009

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