Abstract: This disclosure describes inventions related to the use of biological agents that cause cytokine receptors to be released from the surface of cells. One aspect of this invention is based on the unexpected finding that extending the length of an exemplary agent at the N-terminus enhances expression and production of the product by at least 10-fold. The extended protein can be used to prepare pharmaceutical compositions for treating inflammatory conditions such as rheumatoid arthritis. Another aspect of this invention is based on the identification of biological agents that cause release of cytokine receptors not previously known as natural enzyme targets, such as the IL-1 Type I receptor, IL-1 Type II receptor and the IL-6 receptor. This disclosure provides products, assays, expression systems, purification methods, and production protocols useful for developing cytokine receptor releasing proteins as therapeutic agents.

Abstract: This disclosure provides a new family of proteins implicated in causing the release of TNF receptors and other cytokine receptors from the surface of cells involved in inflammation. Receptor releasing activity was isolated and purified from a monocyte cell line, and sequenced to deduce the gene and protein structure of several different metalloproteases. The information provided in this disclosure enables the user to prepare recombinant protein or expression vectors that will cause receptor release in vivo, thus preventing signal transduction and blocking the effect of incoming cytokines. Medicaments containing cytokine receptor releasing activity are described for use in treating rheumatoid arthritis and other conditions mediated by inflammatory cytokines. The proteins of this invention are all relatively small single-chain molecules, and are therefore easier to use and more cost-effective than other currently marketed biological anti-inflammatory agents.