Interleukin-15

Interleukin-15 (IL-15) is a cytokine of the four-α-helix superfamily that mediates pleiotropic effects in regulating components of both the innate and adaptive immune system. It binds to a heterotrimeric receptor consisting of the common γ-chain receptor, IL-15/IL-2 receptor β-chain and unique IL-15 receptor α-chain. IL-15 is expressed at the mRNA level in a variety of cell lineages and is expressed as protein as part of the rapid early inflammatory response. It mediates activation of NK cells, T cells, neutrophils and macrophages and as such is considered a broad immune activating moiety. IL-15 expression has been described in a variety of inflammatory diseases, including particularly rheumatoid arthritis, psoriatic arthritis and reactive arthritis. Within synovial tissues in particular it has been ascribed an inflammatory role by virtue of its capacity to activate T cells, NK cells macrophages and neutrophils. Moreover, in vivo model studies suggest that IL-15 neutralisation leads to reduction in articular inflammation and damage. Early clinical trials have shown promise in that IL-15 blockade using a monoclonal antibody in rheumatoid arthritis patients lead to some trends to improvement, providing biological proof of concept.