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.
- Arend WP: The innate immune system in rheumatoid arthritis, Arthritis Rheum 44:2224-2234,2001.
- 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.
- 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.
- Arend WP, Malyak M. Guthridge CJ, Gabay C: Interleukin-1 receptor antagonist. Role in biology. Ann Rev Immunol 16:27-55, 1998.
- 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.
- Arend WP: IL-1 receptor antagonist. In Advances in Immunology 54:167-227, 1993.
- 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.
- 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.