Dr. Pine owns stock or stock options in Rigel Pharmaceuticals.
Systemic Lupus Erythematosus
Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice
Article first published online: 10 MAR 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 7, pages 2086–2092, July 2010
How to Cite
Deng, G.-M., Liu, L., Bahjat, F. R., Pine, P. R. and Tsokos, G. C. (2010), Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice. Arthritis & Rheumatism, 62: 2086–2092. doi: 10.1002/art.27452
- Issue published online: 29 JUN 2010
- Article first published online: 10 MAR 2010
- Manuscript Accepted: 26 FEB 2010
- Manuscript Received: 7 JAN 2010
- PHS/NIH. Grant Number: R01-AI-42269
- Mary Kirkland Center for Lupus Research, and Rigel Pharmaceuticals
Spleen tyrosine kinase (Syk) is involved in membrane-mediated signaling in various cells, including immune cells. It is overexpressed in T cells from patients with systemic lupus erythematosus (SLE), and its inhibition has been shown to improve T cell function as well as to improve disease manifestations in (NZB × NZW)F1 lupus-prone mice and in patients with rheumatoid arthritis. While clinical trials examining Syk inhibition in patients with SLE are being considered, the aim of our experiments was to determine whether the therapeutic effects of Syk inhibition extend to other strains of lupus-prone mice and whether they result in improvement in skin disease and modification of established disease.
Female MRL/lpr or BAK/BAX mice were studied. Starting either at age 4 weeks (before disease) or at age 16 weeks (after established disease) and continuing for up to 16 weeks, mice were fed chow containing the Syk inhibitor R788 or control chow.
We found that inhibition of Syk in MRL/lpr and BAK/BAX mice prevented the development of skin disease and significantly reduced established skin disease. Similarly, Syk inhibition reduced the size of the spleen and lymph nodes, suppressed the development of renal disease, and suppressed established renal disease. Discontinuation of treatment resulted in extended suppression of skin disease for at least 8 weeks and suppression of renal disease for 4 weeks.
Syk inhibition suppresses the development of lupus skin and kidney disease in lupus-prone mice, suppresses established disease in lupus-prone mice, and may represent a valuable treatment for patients with SLE.