Targeting the interleukin-15/interleukin-15 receptor system in inflammatory autoimmune diseases.
Interleukin (IL)-15 is a dangerous inflammatory cytokine that induces tumor-necrosis factor-alpha, IL-1beta 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) alpha chain, mutant IL-15, and antibodies directed against the IL-15 cytokine and against the IL-2R/IL-15R beta subunit used by IL-2 and IL-15.
Waldmann
Thomas A
TA
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. tawald@mail.nih.gov
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D019409:Interleukin-15 / Q000502:physiology*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000502:physiology*
C508024:IL15RA protein, human; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2