Editorial

Abstract

This chapter discusses cyclosporins, fungal metabolites with immunosuppressive activities. The fungal metabolite, cyclosporin A [1,2], exerts a powerful immunosuppressive activity directed mainly against T-lymphocytes without affecting haemopoietic tissues. Complementary research activities deal with the development of suitable galenical formulations, the elaboration of analytical methods for monitoring cyclosporin levels, the study of pharmacokinetics and metabolism, and the elucidation of the intriguing mechanism of action of cyclosporin A. In the beginning, cyclosporins were encountered exclusively in Cylindrocapon lucidum and Tolypocladium inflatum. Systematic screening procedures showed later that the related species Tolypocladium geodes as well as several other genera of lower fungi are also capable of synthesizing these secondary metabolites. For large-scale production, aerated submerged cultures of mutants selected from the original strain of T. inflatum were used. C. lucidum, which grows only in surface culture, was less suitable. For inoculum propagation, a yeast-malt agar, and for cultivation, a medium containing glucose and casein peptone supplemented with trace elements and vitamins, is recommended. The main metabolite, cyclosporin A, crystallizes from acetone as white prismatic needles. The lipophilic compound is soluble in most organic solvents but poorly in water.