Use of cytokine expression to predict skin inflammation; methods of treatment

Abstract

Provided are methods for diagnosing the propensity of a subject to develop skin inflammation, in particular, psoriasis. Also provided are methods of treatment with antagonists of IL-17, IL-19, and / or IL-23.

Description

[0001] This application is a Continuation-In-Part application of U.S. patent application Ser. No. 11 / 120,518, filed May 2, 2005, which claims benefit from U.S. Provisional Patent Application No. 60 / 567,747, filed May 3, 2004.FIELD OF THE INVENTION [0002] The present invention relates to methods of analysis the propensity to develop skin inflammatory disorders, in particular, psoriasis. Also provided is a method of treatment to prevent such skin inflammatory disorders using antagonists of IL-17A, IL-17F, IL-19, and / or IL-23. BACKGROUND OF THE INVENTION [0003] The skin serves as an important boundary between the internal milieu and the environment, preventing contact with potentially harmful antigens. In the case of antigen / pathogen penetration, an inflammatory response is induced to eliminate the antigen. This response leads to a dermal infiltrate that consists predominantly of T cells, polymophonuclear cells, and macrophages (see, e.g., Williams and Kupper (1996) Life Sci., 58:1485-...

AI Technical Summary

Benefits of technology

[0012] The present invention also provides a method of preventing skin inflammation comprising administering to a subject exhibiting a propensity to develop skin inflammation: a) an antagonist of IL-17; b) an antagonist of IL-23; c) an antagonist of IL-19; or d) an antagonist of at least two cytokines selected from the group consisting of IL-17, IL-19, or IL-23. In one embodiment the skin inflammation is cutaneous inflammation, in particular, psoriasis. In this method of preventing skin inflammation, subject expresses an average value of at least 5 fold higher IL-17 expression in a non-lesional psoriatic skin sample compared to a normal skin sample, as quantified by real-time PCR. The average value of IL-19 expression is at least 20 fold higher.

[0013] The invention further provides that the antagonist of IL-17, IL-19, and / or IL-23 is an: a) antibody or binding fragment thereof; b) siRNA; or c) a small molecule inhibitor. In a further embodiment, the antibody is: a) a polyclonal antibody; b) a monoclonal antibody; c) a humanized antibody; d) a bi-specific antibody.

Problems solved by technology

In certain cases, this inflammatory response occurs without external stimuli and without proper controls, leading to cutaneous inflammation.

To date, prediction of psoriasis flare-ups has been hampered by lack of knowledge of the cytokine changes between nonlesional and lesional psoriatic tissue.