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

a technology of cytokine and skin inflammation, applied in the field of skin inflammation prediction by cytokine expression, can solve the problems of skin inflammation and hampered prediction of psoriasis flare-up, and achieve the effect of preventing skin inflammation and preventing skin inflammation

Inactive Publication Date: 2005-12-29
SCHERING CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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.

Method used

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examples

I. General Methods.

[0073] Methods for the diagnosis, prevention, and treatment of inflammatory conditions of the skin in animals and humans are described (see, e.g., Ackerman (1997) Histological Diagnosis of Inflammatory Skin Disease, 2nd ed., Lippincott, Williams, and Wilkins, New York, N.Y.; Gallin, et al. (1999) Inflammation:Basic Principles and Clinical Correlates, 3rd ed., Lippincott, Williams, and Wilkins, New York, N.Y.; Parnham, et al. (1991) Drugs in Inflammation (Agents and Actions Suppl., Vol. 32), Springer Verlag, Inc., New York, N.Y.; Chan (ed.) (2003) Animal Models of Human Inflammatory Skin Diseases, CRC Press, Boca Raton, Fla.; Kownatzki and Norgauer (eds.) (1998) Chemokines and Skin, Birkhauser Verlag, Basel, Switzerland; Kanitakis, et al (eds.) (1999) Diagnostic Immunohistochemistry of the Skin, Lippincott, Williams, and Wilkins, New York, N.Y.).

[0074] Animal models of cutaneous inflammation, and related methods, are available. These methods include use of skin ...

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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-...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68
CPCC12Q1/6883C12Q2600/158C12Q1/6881A61K39/3955A61K31/713C12Q2600/106A61P17/00A61P17/06A61P29/00
Inventor KASTELEIN, ROBERTMCCLANAHAN, TERRILLMURPHY, ERINCHAN, JASON
Owner SCHERING CORP
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