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-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-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)-alpha promoter in the murine mast-cell line CPII. It does not, however, affect the human
TNF-alpha promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcgammaRIII 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.