IMMUNOLOGY Cytokine as New Rheumatoid Arthritis Target

Rheumatoid arthritis is a debilitating autoimmune disease characterized by inflammation of the joints that affects millions of people. Joosten et al. report that a recently characterized cytokine, interleukin-32 (IL-32), appears to have an important role in the human disease. Tissue samples from patients with rheumatoid arthritis showed increased expression of IL-32 compared with that in control samples. The abundance of IL-32 correlated with markers of inflammation. Injection of human IL-32 into the knee joint of C57/B16 mice caused swelling and influx of inflammatory cells. IL-32 can induce expression of tumor necrosis factor- (TNF-) in cultured cells, and TNF- is a major contributor to chronic joint inflammation. IL-32 appeared to exert its inflammatory effects through TNF-, because injection of IL-32 failed to cause swelling of joints in TNF- knockout mice. Together, the results from human patients and animal studies lead the authors to conclude that elucidation of mechanisms to reduce activity of IL-32 provides a new strategy for development of therapies that may benefit patients suffering from rheumatoid arthritis.

L. A. B. Joosten, M. G. Netea, S.-H. Kim, D.-Y. Yoon, B. Oppers-Walgreen, T. R. D. Radstake, P. Barrera, F. A. J. van de Loo, C. A. Dinarello, W. B. van den Berg, IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc. Natl. Acad. Sci. U.S.A. 103, 3298-3303 (2006). [Abstract] [Full Text]