CD4+/CD8+ lymphocyte patterns in renal transplant recipients receiving chronic methylprednisolone

Circulating lymphocytes play a major role in mediating allograft rejection. The peripheral lymphocyte count is influenced by methylprednisolone administration, however, the relationship of methylprednisolone pharmacokinetics to lymphocyte trafficking patterns and its effect on selected lymphocyte subsets (CD4+, CD8+) in renal transplant recipients receiving chronic, fixed-doses of this glucocorticoid has not been studied. To examine this relationship, seven stable renal transplant recipients were given their usual oral methylprednisolone dose (mean daily dose = 15 mg) intravenously, and whole blood was obtained over 24 hr. CD4+ and CD8+ cells were quantitated with flow cytometry and serum concentrations of methylprednisolone were analyzed by high performance liquid chromatography (HPLC). Following methylprednisolone administration, a lymphocytopenia was noted in all patients with the CD4+ and CD8+ cells declining to less than 75% of baseline with a resultant nadir at 8 hr. The CD4+ and CD8+ count returned to baseline values by 12 to 24 hr in all patients. Interpatient variability in pharmacokinetic parameters of methylprednisolone was noted with a total body clearance of 240 +/- 112 mL/hr/Kg and half-life ranging from 2.2 to 3.9 hr. The variability seen in the clearance and distribution volume of methylprednisolone among these patients suggests that fixed doses result in a variable degree of systemic exposure. The poor correlation between methylprednisolone pharmacokinetic parameters and the decline of CD4+ and CD8+ cells indicates that other factors may play a role in the lymphocyte trafficking response. Nevertheless, nadir CD4+ and CD8+ cell counts may provide a measure of methylprednisolone immunosuppression in transplant recipients. Studies to examine their relationship to clinical outcomes (i.e., graft function, steroid toxicity, opportunistic infections) are currently in progress.