COMPARATIVE-EVALUATION OF IN-VITRO AND IN-VIVO IMMUNOSUPPRESSIVE POTENTIAL OF CYCLOSPORINE-G WITH CYCLOSPORINE-A AND FK-506

Cyclosporin G (CsG), a promising cyclosporin A (CsA) analogue, was exa mined and compared with two reference immunosuppressive drugs: CsA and FK-506, regarding their inhibitory effects on different lymphocyte ac tivation pathways as well as on graft-versus-host reaction (GvHR) acro ss differences at major or minor histocompatibility loci. The results showed that, at different concentrations, CsG efficiently inhibited pr oliferation induced by alloantigens (mixed lymphocyte culture), mitoge ns (concanavalin A, pokeweed mitogen) and the combination of phorbol m yristate acetate + ionomycin, to the same extent as observed with CsA and FK-506. It was also shown that CsG exhibited the same strong inhib itory effects as the two other immunosuppressants upon stimulation tri ggered by viral (MLs-1(a)) or bacterial (staphylococcal enterotoxin B) superantigen. Determination of IL-2 activity in the supernatant of ML C also confirmed similar strong inhibitory effects, exerted by CsG com pared to CsA. and FK-506. In systemic and local GVHR across major or m inor histocompatibility barriers, CsG as well as CsA and FK-506 presen ted an equivalent immunosuppressive potential. In conclusion, from var ious experiments involving different modes of activation, it was shown that CsG was as strongly immunosuppressive as CsA and FK-506.