IL-1 alpha and IL-1 beta are structurally related polypeptides that show approximately 25% homology at
the amino acid level. Both are synthesized as 31 kDa precursors that are subsequently cleaved into
mature proteins of approximately 17.5 kDa (6, 7). Cleavage of the IL-1 beta precursor by Caspase-1/ICE
is a key step in the inflammatory response (2, 8). Neither IL-1 alpha nor IL-1 beta contains a typical
hydrophobic signal peptide (9-11), but evidence suggests that these factors can be secreted by
non-classical pathways (12, 13). A portion of unprocessed IL-1 alpha can be presented on the cell
membrane and may retain biological activity (14). The precursor form of IL-1 beta, unlike the IL-1 alpha
precursor, shows little or no biological activity in comparison to the processed form (13, 15). Both
unprocessed and mature forms of IL-1 beta are exported from the cell.
IL-1 alpha and IL-1 beta exert their effects through immunoglobulin superfamily receptors that additionally
bind IL-1ra. The 80 kDa transmembrane type I receptor (IL-1 RI) is expressed on T cells, fibroblasts,
keratinocytes, endothelial cells, synovial lining cells, chondrocytes, and hepatocytes (16, 17). The
68 kDa transmembrane type II receptor (IL-1 RII) is expressed on B cells, neutrophils, and bone
marrow cells (18). The two IL-1 receptor types show approximately 28% homology in their
extracellular domains but differ significantly in that the type II receptor has a cytoplasmic domain
of only 29 amino acids (aa), whereas the type I receptor has a 213 aa cytoplasmic domain. IL-1 RII
does not appear to signal in response to IL-1 and may function as a decoy receptor that attenuates
IL-1 function (19). The IL-1 receptor accessory protein (IL-1 RAcP) associates with IL-1 RI and is
required for IL-1 RI signal transduction (20). IL-1ra is a secreted molecule that functions as a
competitive inhibitor of IL-1 (21, 22). Soluble forms of both IL-1 RI and IL-1 RII have been detected
in human plasma, synovial fluids, and the conditioned media of several human cell lines (23, 24). In
addition, IL-1 binding proteins that resemble soluble IL-1 RII are encoded by vaccinia and cowpox
viruses (25).
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