IL15 in Chronic Inflammation

The foregoing description clearly renders IL-15 an intriguing candidate in the context of chronic inflammation. This has now been tested in a number of chronic inflammatory disease states (Table 1). Although expression data pertain to many of these diseases, most functional characterisation has been performed in inflammatory arthritis. We and other groups identified IL-15 and IL-15Ra expression at mRNA and protein levels in inflamed synovium and in peripheral blood from patients with RA (McInnes et al. 1997, 2003). Recently, IL-15 serum expression has been shown to rise progressively with RA disease duration (Gonzalez-Alvaro et al. 2003)]. IL-15 levels are also higher in juvenile idiopathic arthritis and correlate with CRP. IL-15 expression is also reported in RA nodule tissues together with a predominantly Th1 cytokine milieu (Hessian et al. 2003). It is clear therefore that IL-15 is expressed at the site of pathology. The functional importance of IL-15 in inflammatory synovitis is now established. IL-15 enhances synovial T cell proliferation, cytokine release, and optimises cognate interactions between T cells and macrophages that in turn lead to local monokine release including TNFa (McInnes et al. 2000). Additional effects on RA synovial fluid neutrophil activation, synovial NK cell granule release and fibroblast

Table 1. Targeting IL-15 in human disease

Effector function

Disease state

Enhance immune function

Human immunodeficiency virus

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