The Influence of Some Immunosuppressive Drugs on the Metabolic Activity of Human Phagocytes and Lymphocytes in vitro

Abstract

The effect of azathioprine, cyclosporine A and FK 506 on the production of reactive oxygen species by polymorphonuclear leukocytes (Iuminol-dependent chemiluminescence) and on the blast transformation of lymphocytes ([³H]thymidine incorporation) was studied in dose-response experiments under in vitro conditions. Although there were no significant effects of immunosuppressives on non-stimulated blast transformation, FK 506 and cyclosporine A significantly inhibited the blast transformation stimulated by concanavaline A and protein A and the effects made it possible to build 2nd-order polynomial dose-response models. Azathioprine was found to be a relatively weak inhibitor of [³H]thymidine incorporation in lymphocytes (76% of control value). Spontaneous production of reactive oxygen species by polymorphonuclear leukocytes was significantly inhibited, particularly by FK 506 (1–100 ng.ml⁻¹) in comparison to the control value, while there was no effect of the immunosuppressives on this system activated either by starch grains or zymosan. Only the highest applied concentrations of azathioprine (100 ng.ml⁻¹) and cyclosporine A (1000 ng.ml⁻¹) led to a significant decline in spontaneous phagocytosis. The direct effect of immunosuppressives on activated production of reactive oxygen species by neutrophiles was not proved.