Abstract: The present invention relates to the discovery of novel genes encoded by the interleukin-1 locus. The IL-1L1 gene is located in the interval between the IL-1Beta and the IL-1 receptor antagonist encoding genes and encodes a polypeptide which is homologous to both IL-1 agonist and IL-1 antagonist proteins. Therapeutics, diagnostics and screening assays based on these molecules are also disclosed.

Abstract: The invention provides methods and compositions relating to identification and use of genetic information from the IL-1 gene cluster—including the structure and organization of novel IL-1-like genes found within the IL-1 locus as well as polymorphisms and associated haplotypes within these genes. The invention thereby expands the repertoire of useful genetic information available from the IL-1 locus—which contains the previously-identified IL-1&agr;, IL-1&bgr; and IL-1RN genes, for predicting IL-1 associated phenotypes (e.g. increased or decreased risks of inflammatory disease) and for treating IL-1 haplotype associated inflammatory phenotypes.

Abstract: The present provides a mammal in which the expression of one or more interleukin genes has been suppressed. More specifically, the invention concerns the inactivating deletion of the interleukin-1 receptor antagonist gene to produce a knock-out non-human mammal with decreased or completely suppressed expression of the endogenous gene. The invention provides methods for preparing such knock-out mammals and methods of using the knock-out mammals to evaluate the effectiveness of therapeutic agents and regimens to treat diseases or disorders associated with perturbations in the interleukin pathways.