CD4+ CD8+ LYMPHOCYTE PATTERNS IN RENAL-TRANSPLANT RECIPIENTS RECEIVING CHRONIC METHYLPREDNISOLONE/

Circulating lymphocytes play a major role in mediating allograft rejec tion. The peripheral lymphocyte count is influenced by methylprednisol one administration, however, the relationship of methylprednisolone ph armacokinetics to lymphocyte trafficking patterns and its effect on se lected lymphocyte subsets (CD4+, CD8+) in renal transplant recipients receiving chronic, fixed-doses of this glucocorticoid has not been stu died. To examine this relationship, seven stable renal transplant reci pients 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 co ncentrations of methylprednisolone were analyzed by high performance l iquid chromatography (HPLC). Following methylprednisolone administrati on, a lymphocytopenia was noted in all patients with the CD4+ and CD8 cells declining to less than 75% of baseline with a resultant nadir a t 8 hr. The CD4+ and CD8+ count returned to baseline values by 12 to 2 4 hr in all patients. Interpatient variability in pharmacokinetic para meters 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 var iability seen in the clearance and distribution volume of methylpredni solone among these patients suggests that fixed doses result in a vari able degree of systemic exposure. The poor correlation between methylp rednisolone 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 m ay. provide a measure of methylprednisolone immunosuppression in trans plant recipients. Studies to examine their relationship to clinical ou tcomes (i.e., graft function, steroid toxicity, opportunistic infectio ns) are currently in progress.