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A novel anti‐inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology

A novel anti‐inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro... SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti‐inflammatory activity in animal models of allergic contact dermatitis and shows clinical efficacy in atopic dermatitis, allergic contact dermatitis and psoriasis, after topical application. Here we report on the in vitro activities of this promising new drug. SDZ ASM 981 inhibits the proliferation of human T cells after antigen‐specific or non‐specific stimulation. It downregulates the production of Th1 (interleukin (IL)‐2, interferon‐γ) and Th2 (IL‐4, IL‐10) type cytokines after antigen‐specific stimulation of a human T‐helper cell clone isolated from the skin of an atopic dermatitis patient. SDZ ASM 981 inhibits the phorbol myristate acetate/phytohaemagglutinin‐stimulated transcription of a reporter gene coupled to the human IL‐2 promoter in the human T‐cell line Jurkat and the IgE/antigen‐mediated transcription of a reporter gene coupled to the human tumour necrosis factor (TNF)‐α promoter in the murine mast‐cell line CPII. It does not, however, affect the human TNF‐α promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcγRIII receptor. SDZ ASM 981 also prevents the release of preformed pro‐inflammatory mediators from mast cells, as shown in the murine cell line CPII after stimulation with IgE/antigen. In summary, these results demonstrate that SDZ ASM 981 is a specific inhibitor of the production of pro‐inflammatory cytokines from T cells and mast cells in vitro. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Dermatology Wiley

A novel anti‐inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology

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References (47)

Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0007-0963
eISSN
1365-2133
DOI
10.1046/j.1365-2133.1999.02974.x
Publisher site
See Article on Publisher Site

Abstract

SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti‐inflammatory activity in animal models of allergic contact dermatitis and shows clinical efficacy in atopic dermatitis, allergic contact dermatitis and psoriasis, after topical application. Here we report on the in vitro activities of this promising new drug. SDZ ASM 981 inhibits the proliferation of human T cells after antigen‐specific or non‐specific stimulation. It downregulates the production of Th1 (interleukin (IL)‐2, interferon‐γ) and Th2 (IL‐4, IL‐10) type cytokines after antigen‐specific stimulation of a human T‐helper cell clone isolated from the skin of an atopic dermatitis patient. SDZ ASM 981 inhibits the phorbol myristate acetate/phytohaemagglutinin‐stimulated transcription of a reporter gene coupled to the human IL‐2 promoter in the human T‐cell line Jurkat and the IgE/antigen‐mediated transcription of a reporter gene coupled to the human tumour necrosis factor (TNF)‐α promoter in the murine mast‐cell line CPII. It does not, however, affect the human TNF‐α promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcγRIII receptor. SDZ ASM 981 also prevents the release of preformed pro‐inflammatory mediators from mast cells, as shown in the murine cell line CPII after stimulation with IgE/antigen. In summary, these results demonstrate that SDZ ASM 981 is a specific inhibitor of the production of pro‐inflammatory cytokines from T cells and mast cells in vitro.

Journal

British Journal of Dermatology – Wiley

Published: Aug 1, 1999

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