Concentration-dependent effects of prednisolone on lymphocyte subsets and mixed lymphocyte culture in humans

Abstract

In a previous study the feasibility of pharmacokinetic-pharmacodynamic modeling for a quantitative description of the lymphocytopenic effect of prednisolone was demonstrated. We now applied this technique to compare the lymphocytopenia of T-lymphocyte subsets, namely CD8 and CD4. The finding of similar rate constants for the delay of the effect on different T-lymphocyte categories supports the explanation of this delay on the basis of pharmacokinetics rather than cellkinetics. The time course of the responsiveness of remaining lymphocytes in mixed lymphocyte culture after prednisolone administration could be described with the same model as the lymphocytopenia. The concurrence of both effects suggests that total lymphocyte counts, if considered intraindividually, could be used as a measure for monitoring the indirect immunosuppressive effect of prednisolone. The inhibitory effect on mixed lymphocyte culture of plasma from subjects who received prednisolone was directly related with the prednisolone concentrations in plasma. Just as for the indirect effect, a threshold concentration could be observed in the concerning concentration-effect relation. This is attributed to the decrease of endogenous hydrocortisone levels under the influence of prednisolone. Possible consequences of our results and those from related studies for the use of prednisolone as an immunosuppressive drug are discussed.