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.