Inhibitory effect of FK 506 and cyclosporin A on nitric oxide production by LPS-treated cultured rat macrophages

We analyzed the effect of FK 506 on the production of nitric oxide by macro phages. Isolated rat peritoneal macrophages were cultured for 24 h with or without lipopolysaccharide (LPS) (5 mug/ml) and in the absence or presence of FK 506 (0.1 and 1 mug/ml). The concentration of NO2- in culture supernat ants was taken as a measure of nitric oxide production. FK 506 (0.1 and 1 m ug/ml) reduced the LPS-induced increase of NO2- levels by 68% and 81%, resp ectively. The impact of cyclosporin A (CsA) was studied in order to compare their effects. CsA (0.1 and 1 mug/ml) decreased the levels of nitrites by 39% and 69%, respectively. The results obtained suggest that both immunosup pressive drugs exhibit a dose-dependent inhibitory effect on nitric oxide p roduction and that FK 506 is a more potent agent than CsA in this respect.