Interleukin 15 stimulates production of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by human peripheral blood mononuclear cells

In peripheral blood mononuclear cells (PBMC), matrix metalloproteinase (MMP )-9 mediates the extravasation of immune cells and may be involved in tissu e destruction during inflammation. We investigated the effect of the pro-in flammatory cytokines interleukin (IL-)12 and 15 on the secretion of MMP-9 i n PBMC, IL-15, but not IL-12, induces MMP-9 in PBMC and in T cells. Moreove r, the combination of IL-15 and IL-2 had an additive effect. In contrast, b oth IL-12 and IL-15 induced the release of tissue inhibitor of metalloprote inases (TIMP)-1, IL-15 led to a dose-dependent increase of the MMP-9/TIMP-1 ratio as a measure for increased proteolytic capacity, We conclude that IL -15 mediates its effects in inflammation in part through MMP-9. (C) 2001 Ac ademic Press.