targeting the interleukin-15interleukin-15 receptor system in inflammatory autoimmune diseases针对interleukin-15interleukin-15受体系统炎症性自身免疫性疾病.pdfVIP

Arthritis Research Therapy Vol 6 No 4 Waldmann Commentary Targeting the interleukin-15/interleukin-15 receptor system in inflammatory autoimmune diseases Thomas A Waldmann Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Corresponding author: Thomas A Waldmann, tawald@ Received: 31 Mar 2004 Revisions requested: 11 May 2004 Revisions received: 25 May 2004 Accepted: 25 May 2004 Published: 22 Jun 2004 Arthritis Res Ther 2004, 6:174-177 (DOI 10.1186/ar1202) Abstract Interleukin (IL)-15 is a dangerous inflammatory cytokine that induces tumor-necrosis factor-α, IL-1β and inflammatory chemokines. It inhibits self-tolerance mediated by IL-2 mediated activation-induced cell death and facilitates maintenance of CD8+ memory T-cell survival including that of self-directed memory cells. Disordered IL-15 expression has been reported in patients with an array of inflammatory autoimmune diseases. A series of therapeutic agents that inhibit IL-15 action have been introduced, including the soluble IL-15 receptor (IL-15R) α chain, mutant IL-15, and antibodies directed against the IL-15 cytokine and against the IL-2R/IL-15R β subunit used by IL-2 and IL-15. Keywords: autoimmune disease, interleukin-15, memory T cells, rheumatoid arthritis Introduction in such autoimmune diseases as RA, multiple sclerosis, Cytokines are crucially involved in the regulation of the ulcerative colitis, celiac syndrome, psoriasis, sarcoidosis,