Interleukin-18 binding protein: A novel modulator of the Th1 cytokine response

An interleukin-18 binding protein (IL-18BP) was purified from urine by chro matography on IL-18 beads, sequenced, cloned, and expressed in COS7 cells. IL-18BP abolished IL-18 induction of interferon-gamma (IFN gamma), IL-8, an d activation of NF-kappa B in vitro. Administration of IL-18BP to mice abro gated circulating IFN gamma following LPS. Thus, IL-18BP functions as an in hibitor of the early Th1 cytokine response, IL-18BP is constitutively expre ssed in the spleen, belongs to the immunoglobulin superfamily, and has limi ted homology to the IL-1 type II receptor. Its gene was localized on human chromosome 11q13, and no exon coding for a transmembrane domain was found i n an 8.3 kb genomic sequence. Several Poxviruses encode putative proteins h ighly homologous to IL-18BP, suggesting that viral products may attenuate I L-18 and interfere with the cytotoxic T cell response.