In vivo versus in vitro activity of cyclosporine

Cyclosporine (CS) is a relatively new immunosuppressive agent which is selective in its action in that it acts on lymphocytes, T and B cells, and only indirectly if at all on other haemopoietic cells. Numerous studies over the last decade have shown quite clearly that, in vitro, CS inhibits lymphocyte activation at a relatively early stage by preventing the production and release of lymphokines, probably by inhibition of lymphokine gene transcription. However, studies in vivo have produced clearly different findings--although CS in vivo is completely effective in preventing the development of mature effector function (i.e., T-dependent antibody synthesis by B cells or T cell-mediated cytotoxicity) and the consequences of that effector function (e.g., transplant rejection), there is clear evidence that lymphocytes can be activated to at least the stages of cell division and clonal expansion under cover of therapeutic levels of CS. The contradictions between in vitro and in vivo findings are discussed in terms of the possible mechanism of action of CS in vivo.