IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp

IL-18, or IGIF (interferon-gamma inducing factor), is an IL-l-related, pro-inflammatory cytokine, which plays a pivotal role in systemic and local inflammation. We have identified and characterized IL-IH, a novel IL-l-related molecule, IL-1H appears to be expressed in most tissues with relatively high levels in testis, thymus and uterus, The IL-1H transcripts were stimulated by phorbol ester (PMA) in human cell lines (A431, THP-1 and KG-1) and peripheral blood mononuclear cells (HPBMC) and dendritic cells (NHDC), The protein sequence of IL-IH is mostly related to IL-1ra with a similarity of 36%. A short form of IL-1H was identified, and lacks a 40-amino acid segment in the amino-terminal region of the protein. When expressed in mammalian cells, two secreted polypeptides of IL-1H were identified: an uncleaved and a cleaved form starting with amino acid Val-46, Furthermore, IL-1H binds the IL-18 receptor, but not the IL-1 receptor. These findings suggest that IL-IH may be another ligand for the IL-18 receptor and a new player in the inflammatory and immune responses mediated by the IL-18/IL-18R axis. (C) 2001 Academic Press.