Abstract
A novel, water-soluble metabolite of cyclosporine, a sulphate conjugate, present in high concentrations in human bile and plasma was evaluated for its immunosuppressive properties. The direct binding of the conjugate to surface molecules on lymphocytes was studied. The effect of the metabolite was tested in several in vitro systems, including MLR and mitogen-induced proliferation, Il-2 production, generation of CTL, and expression of surface antigens on lymphocytes after stimulation with mitogens. In vivo, the drugs were tested for suppression of the PFC response against SRBC. The results show an inhibitory effect of the conjugate in the generation of CTL and to some extent in the production of Il-2 but not in any of the other systems. The concentrations needed to achieve these effects exceeded those of CsA with a factor of 500-5000.
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