The Mathilda and Terence Kennedy Institute of Rheumatology

The Mathilda and Terence Kennedy Institute of Rheumatology Trust

Fionula Mary Brennan

Marc Feldmann

Patrick William Gray

Martin John Turner

Brian Maurice John Foxwell

A method of identifying a compound with efficacy in the treatment of chronic inflammatory disease by testing the compound for an ability to selectively inhibit the ability of Tcells to induce pro-inflammatory cytokine release from a monocyte is disclosed. The method includes pre-incubatin Tcells with a compound to be tested, optionally resuspending the Tcells in the absence of the test compound, co-culturing the Tcells with monocytes, and assaying for the production of pro-inflammatory cytokines by the monocytes. The Tcells are produced by incubating a population of T cells with one or more cytokines or the Tcells are isolated from synovial tissue. The Tcells have not been contacted with an anti-CD3 antibody. The ability to selectively inhibit cytokine release indicates that the compound has efficacy in the treatment of chronic inflammatory disease.

Method of identifying a compound that selectively inhibits cytokine-stimulated T cell induced production of TNF-alpha by monocytes

A DNA molecule is provided which encodes a polypeptide which is capable of binding human TNF.alpha. and which has the first three cysteine-rich subdomains, but not the fourth cysteine-rich subdomain, of the extracellular binding domain of a receptor selected from the 55 kD and 75 kD receptors for human TNF.alpha.. The ability of the polypeptide to bind to TNF.alpha. means that it can be used for treating diseases mediated by TNF.alpha. activity, such as rheumatoid arthritis.

Nucleic acid encoding modified human tnf.alpha. (tumor necrosis factor

TNF.alpha. receptor-derived binding protein

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Hammersmith, United Kingdom

Fionula Mary Brennan