The in vitro immunosuppressive potency of several therapeutic corticosteroids was investigated using a whole-blood lymphocyte proliferation assay. The selected steroids included beclomethasone dipropionate (BDP), betamethasone (BET), budesonide (BUD), dexamethasone (DEX), flunisolide (FLU), fluticasone propionate (FTP), hydrocortisone (HC), methylprednisolone (MPL), prednisolone (PNL), and triamcinolone acetonide (TAA). The ability of phytohemagglutinin to stimulate lymphocytes in whole blood samples obtained from six drug-free male volunteers was tested against drug concentrations ranging from approximately 0.2 to 2000 nM. Data analysis was conducted employing an inhibitory Hill function and nonlinear regression analysis in ADAPT II. The order of drug concentrations producing 50% inhibition (IC(50)) from highest to lowest was HC > PNL > MPL > BDP > BET > DEX > TAA > FLU > BUD > FTP. These IC(50) values are an inverse measure of drug potency, with FTP representing the most potent corticosteroid examined. A linear correlation was found between the log-transformed 1/IC(50) values and the log of the relative receptor affinity (RRA) values obtained from the literature (r(2) = 0.95). These results extend previous studies to include relatively new corticosteroids and further support the use of RRA values as an indirect measure of relative in vitro immunosuppressive potency.
Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association