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Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer

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Abstract

A patient with renal cell cancer developed acute renal failure due to biopsy-proven acute tubulo-interstitial nephritis (AIN) in the 6th week of continuous infusion of 9 × 106 IU m−2 day−1 recombinant interleukin-2 (rIL-2). We investigated whether the AIN was the result of a cellular cytotoxic reaction induced by the rIL-2 treatment. The cytolytic activity of cryopreserved peripheral blood lymphocytes (PBL), isolated before and at the end of the rIL-2 treatment (at the time of AIN), was studied after 5 days of culture with or without rIL-2 or anti-CD28 and immobilized anti-CD3 antibodies. The PBL isolated before and at the end of the rIL-2 treatment showed cytolytic activity towards a number of allogeneic targets. However, only the PBL isolated at the end of the rIL-2 treatment showed, when stimulated with rIL-2 in vitro, significant cytolytic activity against an autologous renal cell line cultured from the AIN biopsy specimen and against an allogeneic renal cell cancer cell line. These PBL displayed no enhanced killing capacity towards autologous PBL and the melanoma cell line M14. These observations suggest that the AIN may be the result of a cytotoxic lymphocyte-mediated reaction induced by the rIL-2 treatment.

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Author notes

  1. C. J. M. Mellief

    Present address: Department of Immuno-haematology and Blood Bank, Academic Hospital, Rijnsburgerweg 10, 2333 AA, Leiden, the Netherlands

Authors and Affiliations

  1. Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    L. Th. Vlasveld & E. M. Rankin

  2. Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    L. Th. Vlasveld, E. van de Wiel-van Kemenade, A. J. de Boer, J. J. Sein, C. J. M. Mellief, E. M. Rankin, A. Hekman & C. G. Figdor

  3. Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    M. P. W. Gallee

  4. Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands

    R. T. Krediet

Authors
  1. L. Th. Vlasveld
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  2. E. van de Wiel-van Kemenade
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  3. A. J. de Boer
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  7. C. J. M. Mellief
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  9. A. Hekman
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  10. C. G. Figdor
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Vlasveld, L.T., van de Wiel-van Kemenade, E., de Boer, A.J. et al. Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer. Cancer Immunol Immunother 36, 210–213 (1993). https://doi.org/10.1007/BF01741094

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  • DOI: https://doi.org/10.1007/BF01741094

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