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

SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti-inflam matory activity in animal models of allergic contact dermatitis and shows c linical efficacy in atopic dermatitis, allergic contact dermatitis and psor iasis, after topical application. Here we report on the ill vitro activitie s of this promising new drug. SDZ ASM 981 inhibits the proliferation of hum an T cells after antigen-specific or non-specific stimulation. It downregul ates the production of Th1 [interleukin (IL)-2, interferon-gamma] 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-stim ulated 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)-alpha promoter in the murine mast-cell line CPII, It: does not, however, affect t he human TNF-alpha promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the Fc gamma RIII receptor. SDZ ASM 981 also prevents the release of preformed pro-infla mmatory mediators from mast cells, as shown in the murine cell line CPII af ter stimulation with IgE/antigen. In summary, these results demonstrate tha t SDZ ASM 981 is a specific inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro.