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Inhibition of Interleukin 2 (IL-2)-stimulated tyrosine kinase activity by leflunomide

  • Proceedings of the Joint World Congress of the International Association of Inflammation Societies and the European Inflammation Society, Austria Center, Vienna, October 10–15, 1993
  • Imaging Techniques
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Abstract

We have used antigen-specific T-cell clones plus antigen to examine the biochemical effects of leflunomide on T cells during an immune response. Leflunomide inhibited both antigen and IL-2-stimulated proliferation of these clones, with an ED50 of 8–10 μM for either stimuli. Conversely, antigen-stimulated cytokine production and up-regulation of the IL-2 receptor (CD25) were relatively insensitive to inhibition by leflunomide. IL-2-receptor-mediated signaling, however, was inhibited by this drug. Using32P-orthophosphate metabolic labeling and anti-phosphotyrosine immunoprecipitation, we were able to show that leflunomide inhibited IL-2-stimulated tyrosine kinase activity. Furthermore, we demonstrated that leflunomide directly inhibited the IL-2 stimulated tyrosine kinase activity of p56lck. These data suggest that inhibition of IL-2-stimulated p56lck activity could play a role in leflunomide-mediated immunosuppression.

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Authors and Affiliations

  1. Department of Immunology/Microbiology, Section of Transplantation, Rush Presbyterian-St. Luke's Medical Center, 60612, Chicago, IL, USA

    Daniel A Nikcevich, Alison Finnegan, Anita S. -F. Chong & Eric G. Bremer

  2. Department of Internal Medicine, Section of Rheumatology, Rush Presbyterian-St. Luke's Medical Center, 60612, Chicago, IL, USA

    Alison Finnegan

  3. Department of General Surgery, Section of Transplantation, Rush Presbyterian-St. Luke's Medical Center, 60612, Chicago, IL, USA

    Anita S. -F. Chong & James W. Williams

  4. Chicago Institute for Neurosurgery and Neuroresearch, 428 W. Deming Place, 60614, Chicago, IL, USA

    Eric G. Bremer

Authors
  1. Daniel A Nikcevich
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  2. Alison Finnegan
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  3. Anita S. -F. Chong
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  4. James W. Williams
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  5. Eric G. Bremer
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Nikcevich, D.A., Finnegan, A., Chong, A.S.F. et al. Inhibition of Interleukin 2 (IL-2)-stimulated tyrosine kinase activity by leflunomide. Agents and Actions 41 (Suppl 2), C279–C282 (1994). https://doi.org/10.1007/BF01987669

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  • DOI: https://doi.org/10.1007/BF01987669

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