Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2.
The site of action of the immunosuppressive drug cyclosporin A in in vitro cytotoxic allograft responses has been localized. General cytotoxic effects of the drug on proliferating T cells became apparent at concentrations of 500-1000 ng/ml, while selective effects were observed at concentrations of 10-100 ng/ml. The selective effects included a blockade of interleukin 2 release from activated T helper cells on the one hand and inhibition of interleukin 1 release from splenic adherent cells on the other. While cyclosporin A did not interfere with the intracellular events required for the activation and subsequent clonal expansion of alloreactive T cells, the lack of interleukin 1 and interleukin 2 induced by cyclosporin A results in an inability of T responder cells to mount cytotoxic allograft responses in vitro.
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D007376:Interleukin-2; D011506:Proteins