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William P. Arend MD

Professor of Medicine


His laboratory discovered the interleukin-1 receptor antagonist (IL-1Ra) and participated in the purification, cloning and expression of this natural anti-inflammatory protein. IL-1Ra has received FDA approval for the treatment of rheumatoid arthritis and is finding increased use in other systemic inflammatory disorders.

1992-1993 Sabbatical- Visiting Scientist, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO
1980-1981 Sabbatical -Visiting Scientist, Strangeways Research Laboratory, Visiting Scholar, Corpus Christi College, University of Cambridge, Cambridge, England
1969-1971 Fellowship -Department of Medicine, University of Washington School of Medicine, Seattle, WA

1965-1966
&
1968-1969

Residency -Department of Medicine, University of Washington School of Medicine, Seattle, WA

1964-1965

Internship- Department of Medicine, University of Washington School of Medicine, Seattle, WA

Medical School Columbia University College of Physicians and Surgeons, New York City, New York

1993-Present Katherine Elizabeth and David M. Scoville Professor of Rheumatology, University of Colorado School of Medicine, Denver, CO
1981-1983 Professor and Head, Division of Rheumatology, University of Texas School of Medicine, Houston, TX
1983-2000 Head, Division of Rheumatology, University of Colorado School of Medicine,           Denver, CO
1971-1981 Assistant and Associate Professor of Medicine, University of Washington School of Medicine, Seattle, WA
1983 Arrived at University of Colorado School of Medicine

 

 

Member Association of American Physicians
Member American Society for Clinical Investigation
Member American College of Rheumatology
Member American College of Physicians
Member British Society for  Rheumatology
Member Henry Kunkel Society
American College of Rheumatology Board of Directors, Finance Committee, Manpower and Training Committee, Directors of Rheumatology Training Programs, Program Committee (Subsections on Rheumatoid Arthritis, Inflammatory Cytokines and Mediators), Subcommittee on Classification of Vasculitis.
Editor Arthritis and Rheumatism (1995-2000)
Consulting Editor Journal of Clinical Investigation (1992-1995)
Associate Editor Journal of Immunology (1993-1995)
Associate Editor Immunology, Allergy and Rheumatology, Cecil Textbook of Medicine, 22nd edition (2001-present)
National Institutes of Health Member, Advisory Council, National Institute of Arthritis, Musculoskeletal and Skin Diseases (1995-1999)

 

1998 Howley Prize for Research, Arthritis Foundation
1997 Novartis-ILAR Rheumatology Prize
1995 Fellow, American Association for the Advancement of Science
1981 Fellow of the Guggenheim Foundation
1973 Clinical Investigator Award, Veterans Administration

Research interests: Macrophages and cytokines in rheumatoid arthritis. My laboratory discovered the IL-1 receptor antagonist (IL-1Ra) molecule in 1985. In collaborative studies involving my laboratory, the purification and sequencing of this molecule, with cloning and expression of the cDNA, was reported in the journal Nature in 1990. This human protein has been developed as a treatment for patients with rheumatoid arthritis, and was recently approved by the FDA for this indication (Kineret, Amgen). I have continued basic research on IL-1Ra, recently on the function in biology of the intracellular structural variants. These forms of IL-1Ra are created by alternative transcriptional or translational initiation mechanisms, are synthesized in the cytoplasm of selected cells, and generally remain inside cells. Our recent results suggest that the major isoform of intracellular IL-1Ra may interfere with signal transduction pathways responsible for induction of transcription of inflammatory molecules. My laboratory also is studying the effects of complement depletion or treatment with an IL-18 inhibitor on collagen-induced arthritis in mice.

 


Representative publications:

  1. Arend WP:  The innate immune system in rheumatoid arthritis, Arthritis Rheum 44:2224-2234,2001.
     
  2. Arend WP:  Growth factors and cytokiness.  In Primer of the Rheumatic Disease, Twelve Edition, J Klippel, J Stone, CM Weyand, JL Crofford, eds, Arthritis Foundation, Atlanta, GP, pp 58-66, 2001.
     
  3. Gabay C, Marinova-Mutafchieva L, Williams RO, Gigley JP, Butler DM, Feldmann M, Arend WP: Increase production of intracellular interleukin-1 receptor antagonist type 1 (icIL-1Ra1) in the synovium in collegan-induced arthritis in mice.  Arthritis Rehum 44:51-462,2001.
     
  4. Arend WP, Malyak M. Guthridge CJ, Gabay C: Interleukin-1 receptor antagonist.  Role in biology. Ann Rev Immunol 16:27-55, 1998.
     
  5. Gabay C, Smith MF Jr. Eidlen D, Arend WP: Interleukin-1 receptor antagoinist (IL-1Ra) is an acute phase protein. J Clin Invest 99:2930-2940, 1997.
     
  6. Arend WP: IL-1 receptor antagonist. In Advances in Immunology 54:167-227, 1993.
     
  7. Arend WP, Welgus HG, Thompson RC, Eisenberg SP: Biological properties of recombinant human monocyte-derived IL-1 receptor antagonist. J Clin Invest 85:1694-1697, 1990.
     
  8. Arend WP, Joslin FG, Massoni RJ: Effects of immune complexes on production by human monocytes of interleukin 1 or an interleukin 1 inhibitor. J Immunol 134:3868-3875, 1985.