A tissue specific IL-1 receptor antagonist homolog front the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities

Interleukin (Il)-1-like protein 1 (IL-1L1) is a 155-amino acid protein that shares 27% identity with IL-1 beta and 47% with IL-1 receptor antagonist ( IL-1 ra). A 2.7-kb IL-1L1 mRNA was cloned from human placenta and is detect able in the trophoblastic cell line JEG-3, in macrophages and in endotoxin- stimulated monocytes. Expression of IL-1L1 is much less abundant and less w idespread than IL-1ra. We have determined the human and mouse IL-1L1 cDNA s equences and the complete sequence of the human gene, IL1L1. IL1L1 consists of four coding exons, has two alternative non-coding first exons, lies bet ween IL1B and IL1RN, is orientated in the same direction as IL1RN and is se parated from it by similar to 53 kb. The predicted IL-1L1 protein lacks bot h signal sequence and glycosylation signals. A 17-kDa protein was recovered by immunoprecipitation with IL-1L1-specific antibodies from JEG-3. IL-1L1 did not stimulate IL-6 production from primary human fibroblasts or human u mbilical vein endothelial cells nor did it block the IL-1 alpha or IL-1 bet a -dependent activation of IL-6 expression. We conclude, contrary to a rece nt suggestion made by others, that IL-1L1 is not a functional IL-1ra. IL-1L 1 also had no detectable agonistic or antagonistic effect on IFN-gamma prod uction in response to IL-18 in KG-I cells.