[R788: Inhibition of spleen tyrosine kinase suppresses skin and kidney disease in lupus prone mice.
>>Arthritis Rheum. 2010 Mar 10. [Epub ahead of print]
Inhibition of spleen tyrosine kinase suppresses skin and kidney disease in lupus prone mice.
Deng GM, Liu L, Bahjat R, Pine PR, Tsokos GC.
Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02115 USA.
OBJECTIVE.: 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, and improve disease in (NBXNW) F1 mice prone to lupus and patients with rheumatoid arthritis. While Syk inhibition is being considered for clinical trials in patients with SLE, we conducted experiments to determine if its therapeutic effect extends to additional lupus-prone mice, improves skin disease and whether it can modify established disease. METHODS.: Female MRL/lpr or BAX/BAK mice were fed food containing R788 or control food starting either at 4 weeks (prediseased) or 16 weeks (established disease) of age. Mice were fed R788 containing chow for up to 16 weeks. RESULTS.: We demonstrate that inhibition of Syk in MRL/lpr and BAX/BAK mice prevented the development of skin disease and reduced significantly established skin damage. Similarly, Syk inhibition reduced splenomegaly, lymphadenopathy and the development of kidney disease, and suppressed established renal disease. Discontinuation of treatment resulted in extended suppression of skin disease for at least 8 weeks and of renal disease for 4 weeks. CONCLUSION.: Syk inhibition suppresses the development of lupus skin and kidney disease and suppresses established disease in lupus-prone mice and may represent a valuable treatment for patients with SLE.<<
Cheers, Tuck |
