Inhibition of calcineurin activity and protection against cyclosporine A induced cytotoxicity by prednisolone sodium succinate in human peripheral mononuclear cells

We have investigated the effects of prednisolone sodium succinate (Pss) and cyclosporin A (CSA), applied alone or concurrently, on the release of arac hidonic acid (AA) (cytosolic phospholipase A(2) (cPLA(2)) activity) and on the calcineurin (CN) activity of human peripheral blood mononuclear cells ( PBMC). The cytotoxic damage to the cells treated by the drugs was estimated by the release of lactate dehydrogenase (LDH), We found that Pss (10(-5) M ) could inhibit the CN activity and higher concentrations (10(-4) M) could decrease the cytotoxic damage caused by CSA (10(-4) M) during their combine d application. CSA had no specific effect on the release of AA from the cel ls. In the combined clinical use of glutocorticosteroids (GCS) and CSA, the ir additive inhibitory effect on CN activity and the protective membrane in fluence of GCS against the cytotoxicity of CSA may be beneficial, (C) 2000 Elsevier Science B.V. All rights reserved.