INTERLEUKIN-18 INTERFERON-GAMMA-INDUCING FACTOR, A NOVEL CYTOKINE, UP-REGULATES ICAM-1 (CD54) EXPRESSION IN KG-1 CELLS/

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a membrane glycopr otein and a member of the immunoglobulin superfamily, It plays a centr al role I in cell to cell-mediated immune responses and is a ligand fo r leukocyte function-associated antigen-1 (LFA-1), We report here that a newly discovered, cytokine, interferon-gamma-inducing factor (IGIF) [H, Okamura et al, (1995) Nature 378, 88] recently proposed to be des ignated as IL-18, selectively up-regulates ICAM-1 expression in KG-1 c ells, a human myelomonocytic cell line, in which IL-18 also enhances i nterferon-gamma production. IL-18 induced heterotypic aggregation bet tween KG-1 and Peer T cells, which was blocked by anti-ICAM-1 and/or L FA-1 antibodies, Anti-interferon-gamma antibody did not block the IL-1 8-induced up-regulation of ICAM-1 on KG-1 cells. These results thus sh ow that IGIF/IL-18, enhances ICAM-1 expression in KG-l cells in an int erferon-gamma-independent pathway, up-regulates ICAM-1 functions, and that IL-18 might play a potential role in immunoregulation by mediatin g immune cell infiltration into the tissues.